KENILWORTH, N.J., & WOODCLIFF LAKE, N.J.--(BUSINESS WIRE)--Nov 10, 2020--

Merck (NYSE: MRK):

KEYTRUDA (pembrolizumab) Plus LENVIMA (lenvatinib) Demonstrated Statistically Significant Improvement inProgression-Free Survival (PFS), Overall Survival (OS) and Objective Response Rate (ORR) Versus Sunitinib as First-Line Treatment for Patients With Advanced Renal Cell Carcinoma

LENVIMA Plus Everolimus Also Showed Statistically Significant Improvement in PFS and ORR Endpoints Versus Sunitinib

Results of Investigational Phase 3 KEYNOTE-581/CLEAR Trial (Study 307) to be Presented at Upcoming Medical Meeting

Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Eisai today announced new investigational data demonstrating positive top-line results from the pivotal Phase 3 KEYNOTE-581/CLEAR trial (Study 307). In the trial, the combinations of KEYTRUDA, Mercks anti-PD-1 therapy, plus LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, and LENVIMA plus everolimus were evaluated versus sunitinib for the first-line treatment of patients with advanced renal cell carcinoma (RCC). KEYTRUDA plus LENVIMA met the trials primary endpoint of progression-free survival (PFS) and its key secondary endpoints of overall survival (OS) and objective response rate (ORR), demonstrating a statistically significant and clinically meaningful improvement in PFS, OS and ORR versus sunitinib in the intention-to-treat (ITT) study population. LENVIMA plus everolimus also met the trials primary endpoint of PFS and a key secondary endpoint of ORR, demonstrating a statistically significant and clinically meaningful improvement in PFS and ORR versus sunitinib in the ITT study population. The ITT population included patients across all Memorial Sloan Kettering Cancer Center (MSKCC) risk groups (favorable, intermediate and poor). The safety profiles of both KEYTRUDA plus LENVIMA and LENVIMA plus everolimus were consistent with previously reported studies. Merck and Eisai will discuss these data with regulatory authorities worldwide, with the intent to submit marketing authorization applications based on these results, which will be presented at an upcoming medical meeting.

The results for KEYTRUDA plus LENVIMA versus sunitinib, which showed a statistically significant improvement in progression-free survival, overall survival and objective response rate, build on the growing scientific evidence that supports the investigation of KEYTRUDA-based combinations for the first-line treatment of advanced renal cell carcinoma, said Dr. Gregory Lubiniecki, Associate Vice President, Oncology Clinical Research, Merck Research Laboratories. Merck and Eisai are committed to working together to continue to explore the potential of the KEYTRUDA plus LENVIMA combination, particularly in areas of great unmet need such as renal cell carcinoma.

The results from KEYNOTE-581/CLEAR (Study 307) support the potential use of KEYTRUDA plus LENVIMA for the first-line treatment of advanced RCC. These data also support the potential first-line use of LENVIMA plus everolimus, which is already approved in advanced RCC following prior antiangiogenic therapy, said Dr. Takashi Owa, Vice President, Chief Medicine Creation and Chief Discovery Officer, Oncology Business Group at Eisai. These findings energize our efforts as we continue to advance our understanding and address the unmet needs of patients with difficult-to-treat cancers.

Merck and Eisai are continuing to study the KEYTRUDA plus LENVIMA combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program across 19 trials in 13 different tumor types (endometrial carcinoma, hepatocellular carcinoma, melanoma, non-small cell lung cancer, RCC, squamous cell carcinoma of the head and neck, urothelial cancer, biliary tract cancer, colorectal cancer, gastric cancer, glioblastoma, ovarian cancer and triple-negative breast cancer).

About KEYNOTE-581/CLEAR (Study 307)

KEYNOTE-581/CLEAR (Study 307) is a multi-center, randomized, open-label, Phase 3 trial (ClinicalTrials.gov, NCT02811861 ) evaluating LENVIMA in combination with KEYTRUDA or in combination with everolimus versus sunitinib for the first-line treatment of patients with advanced RCC. The primary endpoint is PFS by independent review per RECIST v1.1 criteria. Key secondary endpoints include OS, ORR and safety. The study enrolled approximately 1,050 patients who were randomized to one of three treatment arms to receive:

About Renal Cell Carcinoma (RCC)

Worldwide, it is estimated there were more than 403,000 new cases of kidney cancer diagnosed and more than 175,000 deaths from the disease in 2018. In the U.S. alone, it is estimated there will be nearly 74,000 new cases of kidney cancer diagnosed and almost 15,000 deaths from the disease in 2020. Renal cell carcinoma is by far the most common type of kidney cancer; about nine out of 10 kidney cancers are RCCs. Renal cell carcinoma is about twice as common in men as in women. Most cases of RCC are discovered incidentally during imaging tests for other abdominal diseases. Approximately 30% of patients with RCC will have metastatic disease at diagnosis, and as many as 40% will develop metastases after primary surgical treatment for localized RCC. Survival is highly dependent on the stage at diagnosis, and with a five-year survival rate of 12% for metastatic disease, the prognosis for these patients is poor.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) 10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Endometrial Carcinoma

KEYTRUDA, in combination with LENVIMA, is indicated for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.

Tumor Mutational Burden-High

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barr syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptorblocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.

In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-002, KEYTRUDA was permanently discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). The most common adverse reactions were fatigue (43%), pruritus (28%), rash (24%), constipation (22%), nausea (22%), diarrhea (20%), and decreased appetite (20%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

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KEYTRUDA (pembrolizumab) Plus LENVIMA (lenvatinib) Demonstrated Statistically Significant Improvement in Progression-Free Survival (PFS), Overall...

Cardiac Stem Cells Comments Off on KEYTRUDA (pembrolizumab) Plus LENVIMA (lenvatinib) Demonstrated Statistically Significant Improvement in Progression-Free Survival (PFS), Overall… | November 10th, 2020

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Global Progenitor Cell Product Professional Survey 2020 by Manufacturers, Regions, Types and Applications, Forecast to 2026 - Zenit News

Cardiac Stem Cells Comments Off on Global Progenitor Cell Product Professional Survey 2020 by Manufacturers, Regions, Types and Applications, Forecast to 2026 – Zenit News | November 10th, 2020

Pune, Maharashtra,India, November 9 2020 (Wiredrelease) Origius Systems Private Limited :The increasing occurrence of chronic ailments and obesity all over the world is driving the global biopreservation market growth. The North America region is expected to lead the market growth in the projected period.

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Factors Impacting the Market Growth:

According to the report, growing occurrence of chronic ailments like diabetes, cardiac, degenerative conditions affecting the joints, nerves, bones, and others as well as obesity all over the world are thrusting the demand for biopreservation techniques, which is fueling the growth of the market. Additionally, the increasing investments in R&D and development of advanced biopreservation products is expected to unlock rewarding opportunities for the market growth. However, greater costs involved in biopreservation processes, reliability concerns, and invention of low-priced processes are likely to detain the biopreservation market growth.

Segment Analysis:

The report segments the biopreservation market into type, biospecimen, application, end use, and region.

Based on biospecimen, the report divides the market into: Stem Cells Human Tissue Organs

Among these, the human tissue segment is expected to witness highest growth in the biopreservation market all through the projected period; mainly due to rising cases of chronic ailments, degenerative disorders, and obesity.

Based on application, the report classifies the market into: Therapeutic Research Clinical Trials

Among these, the therapeutic segment is projected to show noteworthy growth during the forecast period. This is mainly owing to the developments in treatment techniques, personalized drugs, regenerative drugs, increasing trend for cord blood banking, and increasing occurrence of chronic ailments worldwide.

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Regional Analysis:

The report states the scenario of the global biopreservation market across several regions including: Europe LAMEA North America Asia Pacific

Among these, the North America region is projected to grab the highest market share of the biopreservation market in the forecast period. This is attributed to the growing awareness about personalized drugs, rising R&D in regenerative medicines, increasing prevalence of obesity, and chronic ailments.

Market Players and Business Strategies:

The report cites some of the leading players in the global biopreservation market which includes: Avantor, Inc. Bio-Techne Exact Sciences Corporation Merck KGaA ThermoGenesis Corp. BioLifeSolutions Inc. BioCision Chart Industries Thermo Fisher Scientific Inc. Worthington Industries, Inc.

The report highlights some of the wining business strategies of the players such as mergers and acquisitions, ground-breaking advances, geographical expansions, new product inventions, and many more.Quick Download Top Companies Development Strategies Summary Report

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Advancement: Know the Rapid Growth Factors of Biopreservation Market| Stay Up-To-Date With Emerging - PharmiWeb.com

Cardiac Stem Cells Comments Off on Advancement: Know the Rapid Growth Factors of Biopreservation Market| Stay Up-To-Date With Emerging – PharmiWeb.com | November 10th, 2020

Global Mesenchymal Stem Cells market report 2020 offers extremely oblique professional analysis and forecast from 2020 to 2026. The report also consists of market shares, size, profit revenue, and the Mesenchymal Stem Cells markets economic process. It also covers the strategic identification of major players within the market and analyzing their core competencies and methodology. The Mesenchymal Stem Cells market report analyzes information collected and integrated through recent analysis techniques and from trustful sources across varied industries.

A thorough evaluation of the restrains encompassed in the Mesenchymal Stem Cells report reveals the difference to drivers and contributes room for strategic planning. Features that overshadow the Mesenchymal Stem Cells market development are essential. They can be understood to devise different bends for getting hold of the profitable prospects present in the ever-growing market. Additionally, perceptions by market expert opinions have been taken to understand the Mesenchymal Stem Cells market better.

[Due to the pandemic, we have included a special section on the Impact of COVID 19 on the market which would mention How the Covid-19 is Affecting the Global Mesenchymal Stem Cells Market]

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Top Key Players of Mesenchymal Stem Cells Market:

(Celprogen Inc., Axol Bioscience Ltd., Stemedica Cell Technologies Inc., Cell Applications Inc., Stem cell technologies Inc., Cytori Therapeutics Inc., Cyagen Biosciences Inc., BrainStorm Cell Therapeutics.)

On the basis of Types, the Mesenchymal Stem Cells market:

Bone Marrow Umbilical Cord Blood Peripheral Blood Lung Tissue Synovial Tissues Amniotic Fluids Adipose Tissues

On the basis of Applications, the Mesenchymal Stem Cells market:

Injuries Drug Discovery Cardiovascular Infraction Others

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Geographically, the detailed analysis of consumption, revenue, market share and growth rate, historic and forecast (2016-2026) of the following regions are including,

The Research aims of the Mesenchymal Stem Cells Market report would be:

Major TOC points

1Mesenchymal Stem Cells Market Overview

1.1 Product Overview and Scope of Mesenchymal Stem Cells

1.2 Segment by Type

1.2.1 Global Sales Growth Rate Comparison by Type (2021-2026)

1.2.2 Type 1

1.2.3 Type 2

1.3 Segment by Application

1.3.1 Sales Comparison by Application: 2020 VS 2026

1.3.2 Application 1

1.3.3 Application 2

1.4 Global Market Size Estimates and Forecasts

1.4.1 Global Revenue 2016-2026

1.4.2 Global Sales 2016-2026

1.4.3 Mesenchymal Stem Cells Market Size by Region: 2020 Versus 2026

2 Global Mesenchymal Stem Cells Market Competition by Manufacturers

2.1 Global Sales Market Share by Manufacturers (2016-2020)

2.2 Global Revenue Share by Manufacturers (2016-2020)

2.3 Global Average Price by Manufacturers (2016-2020)

2.4 ManufacturersMesenchymal Stem Cells Manufacturing Sites, Area Served, Product Type

2.5 Market Competitive Situation and Trends

2.5.1 Mesenchymal Stem Cells Market Concentration Rate

2.5.2 Global Top 5 and Top 10 Players Market Share by Revenue

2.5.3 Market Share by Company Type (Tier 1, Tier 2, and Tier 3)

2.6 Manufacturers Mergers and Acquisitions, Expansion Plans

2.7 Primary Interviews with KeyMesenchymal Stem Cells Players (Opinion Leaders)

3 Mesenchymal Stem Cells Retrospective Market Scenario by Region

3.1 Global Mesenchymal Stem Cells Retrospective Market Scenario in Sales by Region: 2016-2020

3.2 Global Mesenchymal Stem Cells Retrospective Market Scenario in Revenue by Region: 2016-2020

3.3 North America Market Facts and Figures by Country

3.4 EuropeMesenchymal Stem Cells Facts and Figures by Country

3.5 Asia Pacific Market Facts and Figures by Region

3.6 Latin America Market Facts and Figures by Country

3.7 the Middle East and Africa Market Facts and Figures by Country

4 Global Mesenchymal Stem Cells Historic Market Analysis by Type

4.1 Global Sales Market Share by Type (2016-2020)

4.2 Global Revenue Market Share by Type (2016-2020)

4.3 Global Price Market Share by Type (2016-2020)

4.4 Global Market Share by Price Tier (2016-2020)

5 GlobalMesenchymal Stem Cells Historic Market Analysis by Application

5.1 Global Sales Market Share by Application (2016-2020)

5.2 Global Revenue Market Share by Application (2016-2020)

5.3 Global Price by Application (2016-2020)

..Countinued

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Mesenchymal Stem Cells Market to Witness Significant Rise in Revenue and Covid-19 Impact by 2026 | Celprogen Inc., Axol Bioscience Ltd., Stemedica...

Bone Marrow Stem Cells Comments Off on Mesenchymal Stem Cells Market to Witness Significant Rise in Revenue and Covid-19 Impact by 2026 | Celprogen Inc., Axol Bioscience Ltd., Stemedica… | November 8th, 2020

The recent study on the Autologous Stem Cell Based Therapies market offers a competitive advantage to organizations operating in this industry vertical through a comprehensive assessment of the present and future growth prospects.

The report explicates important facets such as primary growth catalysts, and opportunities that will ensure the revenue flow in the coming years. Further, it lists the challenges and limitations along with solutions to overcome them. Insights germane to the market share and growth rate estimates of the industry segments are also provided as well.

Apart from this, the study delves into the business scenario across the various regional markets and profiles the companies that have reigned in these geographies. Further, it highlights the prevalent strategies adopted by leading companies while simultaneously suggesting changes and new tactics for adapting to the uncertainties brought in by the Covid-19 pandemic.

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Key pointers from the TOC of the Autologous Stem Cell Based Therapies market report:

Product gamut

Application scope

Regional outlook

Competitive landscape

In conclusion, the study systematically investigates the Autologous Stem Cell Based Therapies market through various segments to provide a broad view of this business sphere. In addition, it expounds the supply chain in terms of distributors, downstream consumers, and upstream material and equipment traders in this industry.

Reasons to access this Report:

The key questions answered in this report:

Significant Point Mentioned in theResearch report:

Table of Contents for market shares by application, research objectives, market sections by type and forecast years considered:

Autologous Stem Cell Based Therapies Market Share by Key Players: Here, capital, revenue, and price analysis by the business are included along with other sections such as development plans, areas served, products offered by key players, alliance and acquisition and headquarters distribution.

Global Growth Trends: Industry trends, the growth rate of major producers, and production analysis are the segments included in this chapter.

Market Size by Application: This segment includes Autologous Stem Cell Based Therapies market consumption analysis by application.

Autologous Stem Cell Based Therapies market Size by Type: It includes analysis of value, product utility, market percentage, and production market share by type.

Profiles of Manufacturers: Here, commanding players of the global Autologous Stem Cell Based Therapies market are studied based on sales area, key products, gross margin, revenue, price, and production.

Autologous Stem Cell Based Therapies Market Value Chain and Sales Channel Analysis: It includes customer, distributor, market value chain, and sales channel analysis.

Market Forecast: This section is focused on production and production value forecast, key producers forecast by type, application, and regions

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Autologous Stem Cell Based Therapies Market 2020 Emerging Trend and Advancement - News by aeresearch

Cardiac Stem Cells Comments Off on Autologous Stem Cell Based Therapies Market 2020 Emerging Trend and Advancement – News by aeresearch | November 8th, 2020

This article was originally published here

Cell Mol Neurobiol. 2020 Nov 5. doi: 10.1007/s10571-020-00989-x. Online ahead of print.

ABSTRACT

This article reviews the wealth of papers dealing with the different effects of epidermal growth factor (EGF) on oligodendrocytes, astrocytes, neurons, and neural stem cells (NSCs). EGF induces the in vitro and in vivo proliferation of NSCs, their migration, and their differentiation towards the neuroglial cell line. It interacts with extracellular matrix components. NSCs are distributed in different CNS areas, serve as a reservoir of multipotent cells, and may be increased during CNS demyelinating diseases. EGF has pleiotropic differentiative and proliferative effects on the main CNS cell types, particularly oligodendrocytes and their precursors, and astrocytes. EGF mediates the in vivo myelinotrophic effect of cobalamin on the CNS, and modulates the synthesis and levels of CNS normal prions (PrPCs), both of which are indispensable for myelinogenesis and myelin maintenance. EGF levels are significantly lower in the cerebrospinal fluid and spinal cord of patients with multiple sclerosis (MS), which probably explains remyelination failure, also because of the EGF marginal role in immunology. When repeatedly administered, EGF protects mouse spinal cord from demyelination in various experimental models of autoimmune encephalomyelitis. It would be worth further investigating the role of EGF in the pathogenesis of MS because of its multifarious effects.

PMID:33151415 | DOI:10.1007/s10571-020-00989-x

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Epidermal Growth Factor in the CNS: A Beguiling Journey from Integrated Cell Biology to Multiple Sclerosis. An Extensive Translational Overview -...

Spinal Cord Stem Cells Comments Off on Epidermal Growth Factor in the CNS: A Beguiling Journey from Integrated Cell Biology to Multiple Sclerosis. An Extensive Translational Overview -… | November 8th, 2020

Adipose tissue is rich in multi potent stem cells that have the capability to differentiate into a number of cell types including adipocytes, osteocytes, chondrocytes and others, in vitro. These Adipose Tissue-derived Stem Cells are used for a number of applications including stem cell differentiation studies, regenerative medicine, cell therapy, tissue engineering and development of induced pluripotent stem cell lineage. Adult stem cells such as the Adipose Tissue-derived Stem Cells have a very good potential for regenerative medicine. The Adipose Tissue-derived Stem Cells show higher yields compared with other stem cell sources. Some of the regenerative medicine applications using Adipose Tissue-derived Stem Cells include skin, bone and cartilage regeneration.

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Although, Adipose Tissue-derived Stem Cells have the ability to differentiate into different cell types in vitro, unlike the embryonic stem cells they lack the ability to differentiate into all types of organs and tissues of the body. Derivation of stem cells from adipose tissue have a number of advantages including that fat tissue contain 100 to 1000 times more mesenchymal stem cells than the bone marrow. Furthermore the method of collection of fat tissue is relatively easier and is less invasive than that of bone marrow collection. Although Adipose Tissue-derived Stem Cells have a potential to be used in cell-based therapy, there are a number of challenges the Adipose Tissue-derived Stem Cells market has to face. Some of the challenge include the safety issue for the clinical use of Adipose Tissue-derived Stem Cells, development and differentiation of the cells, delivery of the cells in vivo and immune response after the transplant.

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The global Adipose Tissue-derived Stem Cells market is segmented based on product type and end user. Based on product type the Adipose Tissue-derived Stem Cells can be categorized into cell line and reagent & kits. Cell line can be further classified based on the source of the adipose tissue such as human and rodents. Based on reagents the Adipose Tissue-derived Stem Cells market is further classified as media & sera and kits. Based on application the Adipose Tissue-derived Stem Cells market is classified into regenerative medicine, cell therapy, tissue engineering, and other applications such as cell differentiation studies and other similar research. End users of Adipose Tissue-derived Stem Cells market are biotechnology companies and academic and research institutes.

The Global Adipose Tissue-derived Stem Cells market is classified on the basis of product type, end user and region:

Based on the Product Type, Adipose Tissue-derived Stem Cells market is segmented into following:

Based on the application, Adipose Tissue-derived Stem Cells market is segmented into following:

Based on the end user, Adipose Tissue-derived Stem Cells market is segment as below:

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Growing research activities using stem cells along with the growth of regenerative medicine and cell therapy the global Adipose Tissue-derived Stem Cells market is set to expand considerably during the forecast period. However, ethical concerns and stringent regulations may hinder the growth of the global Adipose Tissue-derived Stem Cells market.

On the basis of geography, global Adipose Tissue-derived Stem Cells market is segmented into six major regions that include North America, Latin America, Europe, Asia-Pacific excluding China, China and Middle East & Africa. North America is expected to be the most lucrative Adipose Tissue-derived Stem Cells market owing to increased research activity of stem cells. Furthermore government support for regenerative and stem cell based studies along with cell therapy studies is driving the growth of the Adipose Tissue-derived Stem Cells market in the region. Changing government regulations in china is supporting the research activity that supports the growth of the adipose tissue-derived stem cell market in the region at a considerable rate.

Key participants operating in the Adipose Tissue-derived Stem Cells market are: Lonza, ThermoFisher Scientific, Celprogen, Inc, American CryoStem, Rexgenero Ltd, iXCells Biotechnologies, Merck KGaA, Lifeline Cell Technology, and others.

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The Adipose Tissue Derived Stem Cells market to grow in the wake of incorporation of the latest technology - The Think Curiouser

Skin Stem Cells Comments Off on The Adipose Tissue Derived Stem Cells market to grow in the wake of incorporation of the latest technology – The Think Curiouser | November 8th, 2020

Trusted Business Insights answers what are the scenarios for growth and recovery and whether there will be any lasting structural impact from the unfolding crisis for the Cell Expansion market.

Trusted Business Insights presents an updated and Latest Study on Cell Expansion Market 2020-2029. The report contains market predictions related to market size, revenue, production, CAGR, Consumption, gross margin, price, and other substantial factors. While emphasizing the key driving and restraining forces for this market, the report also offers a complete study of the future trends and developments of the market.The report further elaborates on the micro and macroeconomic aspects including the socio-political landscape that is anticipated to shape the demand of the Cell Expansion market during the forecast period (2020-2029).It also examines the role of the leading market players involved in the industry including their corporate overview, financial summary, and SWOT analysis.

Get Sample Copy of this Report @ Cell Expansion Market 2020 and Forecast 2021-2027 Includes Business Impact Analysis of COVID-19

Report Overview: Cell Expansion Market

The global cell expansion market size was estimated at USD 18.1 billion in 2020 is expected to register a compound annual growth rate (CAGR) of 8.3% over the forecast period 2021-2027. Increase in usage of automated solutions in cell expansion applications is one of the market drivers. Automated systems minimize the manpower and cost incurred during the production of Cell Therapy Products (CTP), gene therapies, and other biologics; leading to robust and reliable processes.

Key players engaged in CTP development are expanding their product line to suffice the significant rise in the global demand for these therapy products. For instance, in March 2019, Lonza introduced a comprehensive portfolio of CellBio Services, which includes cell-line expansion and banking services. This solution is designed to fulfill research application requirements, finally accelerating the revenue generation in the market.

The paradigm shift toward Single-Use Systems (SUS) offers substantial production advantages in CTP manufacturing. SUS eliminates concerns of cross-contamination and culture contamination caused due to inappropriate sterilization. SUS also allows the production of CTP with high cell densities as well as offers cost-savings in the long run. Thus, a rise in the adoption of SUS surges the development of CTP, which boosts the market growth.

Cellular therapies are constantly gaining popularity in the life sciences industry. Rise in funding from private & government organizations and initiatives undertaken by them to encourage the development of cellular therapies act as drivers for the market. The International Society for Stem Cell Research is involved in the identification of stem cell-related funding opportunities across biomedical research applications.

Substitution of serum and other incompatible reagents is essential to control the quality of the product in CTP manufacturing. Several research studies have validated that the application of serum-free media controls product quality. Researchers have also developed an optimization platform that integrates high-throughput tools with a differential evolution-based algorithm, which acts as an automated effective optimization strategy for serum-free culture formulations.

Product Insights: Cell Expansion Market

Consumables led the product segment in 2019 and accounted for 46.8% of the overall share. It is estimated to retain its dominant position throughout the forecast years. Availability of a wide range of commercial media and reagent products that are dedicated to specific type of cells contributes to the large revenue share of this segment. In addition, these products are convenient, ready-to-use, and are also available as serum-free formulations.

The instruments segment is expected to register the highest CAGR over the forecast period owing to automation in bioreactors and other expansion platforms to enhance the efficiency of culturing procedures. The advent of automated platforms standardizes the process and facilitates process tracking while reducing the hands-on time; therefore, enables more effective use of the time of skilled personnel.

Continuous commercialization and introduction of automated culturing equipment also drive the revenue generation in the instruments segment. For instance, in March 2019, Hitachi, Ltd. commercialized its automated cell mass culture equipment in Japan. This commercialization allowed manufacture of induced pluripotent stem cells for regenerative medicine applications. Such efforts are expected to accelerate the revenue generation for instruments.

Cell Type Insights: Cell Expansion Market

Mammalian cells segment held the largest revenue share of 58.5% in 2019 and will remain dominant during the forecast period as these culture systems are highly preferred in production of complex protein therapeutics. This is because these systems are pharmacokinetically and functionally relevant to post-translational modifications in humans. Therefore, most of the biopharmaceuticals, including monoclonal antibodies, specific interferons, thrombolytics, and various therapeutic enzymes, are produced using these culture systems.

Differentiated human cells accounted for substantial revenue share as these cells perform a specific function in the body. Differentiated cells, such as fibroblasts, have gained immense importance in the cutaneous wound healing and skin bioengineering, thereby augmenting the segment growth. Moreover, evaluation of 3D Gingival Fibroblast (GF) toroids as a feasible and simple in vitro assay for biomaterial testing has expanded their usage rate.

Human stem cells have gained significant traction and are expected to witness the fastest CAGR from 2020 to 2027. The exponential growth of research in this sector and the huge success of regenerative medicine are among the key factors that can be attributed to the fastest growth rate. Furthermore, implementation of automated, robotic, and closed production systems in the manufacturing of clinical-grade mesenchymal stem cells drives the segment.

Application Insights: Cell Expansion Market

The biopharmaceutical segment captured the largest revenue share of 22.9% in 2019 owing to increase in the approvals of biopharmaceutical products in the past few years. The entry of new biopharmaceutical companies and the proliferation of bioprocessing technologies further drive the development of biopharmaceuticals, which, in turn, boosts the expansion procedures conducted during bio-production.

In addition, single-use technologies are gaining immense traction in manufacturing cellular therapies on a commercial level. The introduction of alternative planar cell expansion technologies, such as compact multi-layer bioreactors, has been witnessed over the years. This sufficed the requirement of closed systems that limits the potential risks associated with contamination and maintains control of a large-scale upstream production and unit production.The vaccine production segment is expected to witness the fastest growth rate during the forecast period due to the expansion of cell-based vaccine production in recent years. The production of these vaccines offers a cost-effective manufacturing solution while accelerating the development process.

End-use Insights: Cell Expansion Market

Biotechnology & biopharmaceutical companies segment held the largest share of 48% in 2019 and will expand further at a significant growth rate. The broadening horizon of cell-based therapeutics in the healthcare industry is one of the major factors contributing to the large share of biopharmaceutical companies. For instance, cellular-based therapies have gained immense popularity in regenerative medicine with constant improvements in injectable cell delivery systems for various clinical applications.

In addition, pharmaceutical & biopharmaceutical companies are also engaged in acquisitions to expand their product portfolio. For instance, in December 2019, Sartorius AG signed an agreement to acquire 50% shares of Biological Industries, an Israeli cell culture media manufacturer. This acquisition expanded the cell culture media portfolio of Sartorius, especially for cellular and gene therapies, regenerative medicine, and other advanced therapies.

Research institutes are anticipated to register the highest CAGR from 2020 to 2027 as researchers are engaged in several studies in the biomedical field. For instance, in April 2019, researchers at the University of Wisconsin, U.S., introduced a new technology for effortless development of the H3N2 vaccine. For this, they developed a new cell line that enhanced the growth of H3N2 for vaccine use. Such research findings are expected to help in introducing new products in this market.

Regional Insights: Cell Expansion Market

North America accounted for the largest share of 43.1% in 2019. The region will retain its leading position over the coming years due to a rise in funding initiatives by the government agencies, which has accelerated the manufacture of stem cells and the development of regenerative medicine and cellular therapy products. This, in turn, drives the demand for cell expansion platforms in this region.

For instance, in October 2019, the FDA and the Medical Technology Enterprise Consortium (MTEC) together provided funding of USD 5.3 million to the Southwest Research Institute (SwRI) (U.S.). The SwRI invested these funds to propagate cells for the development of personalized regenerative medicine. Such investments boost the revenue generation in this region.

Asia Pacific is expected to witness the fastest growth during the forecast period due to increasing efforts laid down by several local pharmaceutical and biotechnology companies to develop and commercialize their cellular therapies. An Indian company, Stempeutics Research Pvt. Ltd., signed an alliance with Kemwell Biopharma in July 2019 for the commercialization of its stem cell-based product, Stempeucel. Such agreements are expected to boost product sales of small- and mid-scale companies.

Key Companies & Market Share Insights: Cell Expansion Market

Key market participants are undertaking several initiatives to expand their market presence and maintain a competitive edge in the space. Moreover, they are involved in collaboration & partnership models, product development, agreements, and business expansion strategies in untapped regions.

For instance, in June 2019, Demcon acquired a share in the Scinus Cell Expansion B.V., a manufacturer of stem cell-based therapy equipment headquartered in the Netherlands. This acquisition helped Scinus to expand its business in the stem cell therapy market. Such growth initiatives are expected to enhance the utilization rate of bioreactors used for culturing stem cells, thereby leading to market growth. Some of the prominent players in the cell expansion market include:

Key companies Profiled: Cell Expansion Market Report

This report forecasts revenue growth at global, regional, and country levels and provides an analysis of the latest industry trends in each of the sub-segments from 2016 to 2027. For the purpose of this study, Trusted Business Insights has segmented the global cell expansion market report on the basis of product, cell type, application, end use, and region:

Product Outlook (Revenue, USD Million, 2016 2027)

Cell Type Outlook (Revenue, USD Million, 2016 2027)

Application Outlook (Revenue, USD Million, 2016 2027)

End-use Outlook (Revenue, USD Million, 2016 2027)

Looking for more? Check out our repository for all available reports on Cell Expansion in related sectors.

Quick Read Table of Contents of this Report @ Cell Expansion Market 2020 and Forecast 2021-2027 Includes Business Impact Analysis of COVID-19

Trusted Business InsightsShelly ArnoldMedia & Marketing ExecutiveEmail Me For Any ClarificationsConnect on LinkedInClick to follow Trusted Business Insights LinkedIn for Market Data and Updates.US: +1 646 568 9797UK: +44 330 808 0580

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Cell Expansion Market Analysis, COVID-19 Impact,Outlook, Opportunities, Size, Share Forecast and Supply Demand 2021-2027|Trusted Business Insights -...

Skin Stem Cells Comments Off on Cell Expansion Market Analysis, COVID-19 Impact,Outlook, Opportunities, Size, Share Forecast and Supply Demand 2021-2027|Trusted Business Insights -… | November 8th, 2020

Medical skin care products are used for beautifying or to address some other skin care problems. The cosmetic industry is booming and skin care forms a very huge part of this industry. The aesthetic appearance is so important that people spend a lot on skin care products and treatment. People being more technologically aware of the various new skin care products trending in the market. In addition to the aesthetic application, the medical skin care products are also used to address issues such as acne, pimples or scars.

Medical Skin Care Products Market: Drivers and Restraints

The medical skin care products is primarily driven by the need of natural based active ingredients products which are now trending in the market. Consumers demand medical skin care products which favor health and environment. Moreover, the consumers are updated with the trends so that various companies end up providing such products to satisfy the customers. For instance, a single product face mask has thousands of different variants. This offers consumers different options to select the product depending on the skin type. Moreover, the market players catering to the medical skin care products are offering products with advanced technologies. For instance, Santinov launched the CICABEL mask using stem cell material based on advanced technologies. The stem cells used in the skin care product helps to to protect and activate the cells and promote the proliferation of skin epidermal cells and the anagenesis of skin fibrosis.

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Medical Skin Care Products Market: Segmentation

On the basis of product type the medical skin care products market can be segmented as:

On the basis of application, the medical skin care products market can be segment as:

On the basis of distribution channel, the medical skin care products market can be segment as:

Medical Skin Care Products Market: Overview

Medical skin care products are used to address basic skin problems ranging from acne to scars. There are various advancements in the ingredients used to offer skin care products to the consumers. For instance, the use of hyaluronic acid and retinoids is the latest development in the industry. The anti-aging creams are at the forefront as the help treating issues such as wrinkles, scars, acne, and sun damage. Another, product in demand is the probiotic skincare which include lactobacillus and bifidobacterium.

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Medical Skin Care Products Market: Region-wise Outlook

In terms of geography, medical skin care products market has been divided into five regions including North- America, Asia- Pacific, Middle-East & Africa, Latin America and Europe. North America dominated the global medical skin care products market as international players are acquiring domestic companies to make their hold strong in the U.S. LOral is accelerating its U.S. market by signing a definitive agreement with Valeant Pharmaceuticals International Inc. to acquire CeraVe, AcneFree and Ambi skin-care brands for US$ 1.3 billion. The acquisition is expected LOreal to get hold of the brands in the price-accessible segment. Asia Pacific is expected to be the fastest growing region owing to the increasing disposable income and rising awareness towards the skin care products.

Medical Skin Care Products Market: Key Market Participants

Some of the medical skin care products market participants are Avon Products Inc., Beiersdorf AG, Colgate-Palmolive Company, Kao Corporation, LOral S.A., Procter & Gamble, Shiseido Company, The Estee Lauder Companies Inc., Unilever PLC, Revlon, Clinique Laboratories, llc., Murad, LLC., SkinCeuticals, RMS Beauty, J.R. Watkins and 100% PURE.

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The Medical Skin Care Products Market to witness non-linear transition from 2017 to 2025 - PRnews Leader

Skin Stem Cells Comments Off on The Medical Skin Care Products Market to witness non-linear transition from 2017 to 2025 – PRnews Leader | November 5th, 2020

According to IMARC Groups latest report, titled Regenerative Medicine Market: Industry Trends, Share, Size, Growth, Opportunity and Forecast 2020-2025,. Looking forward, IMARC Group expects the global regenerative medicine market to continue its strong growth during the next five years.

Regenerative medicine refers to a field of biomedical sciences involved in restoring the structure and function of damaged cells, organs, and tissues. It includes the study of stem cells that are developed in laboratories and then safely inserted into the human body to regenerate damaged bones, cartilage, blood vessels, and organs. Cellular and acellular regenerative medicines are widely adopted in various clinical therapeutic procedures, including cell therapies, immunomodulation, and tissue engineering. They have the potential to treat various chronic diseases, including Alzheimers, Parkinsons, cardiovascular disorders (CVDs), osteoporosis, spinal cord injuries, etc.

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Market Trends

The rising prevalence of chronic diseases and genetic disorders is primarily driving the demand for regenerative medicine across the globe. Moreover, the growing geriatric population who are more prone to musculoskeletal, dermatological, and cardiological disorders is also augmenting the need for regenerative medicines. Furthermore, several technological advancements in cell-based therapies have led to the adoption of 3D bioprinting techniques and artificial intelligence (AI), thereby further propelling the market for regenerative medicine. Moreover, regenerative medicine decreases the risk of organ rejection by the body post-transplant and increases the patients recovery speed, thereby gaining traction in numerous organ transplantation procedures. The increasing investments in extensive R&D activities in the field of medical sciences are expected to drive the market for regenerative medicine.

Regenerative Medicine Market 2020-2025 Analysis and Segmentation:

Competitive Landscape:

The competitive landscape of the market has been studied in the report with the detailed profiles of the key players operating in the market.

Some of these key players include:

The report has segmented the market on the basis of type, application, end user and region.

Breakup by Type:

Breakup by Application:

Breakup by End User:

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Regenerative Medicine Market 2020: Analysis, Top Companies, Size, Share, Demand and Opportunity To 2025 - Eurowire

Spinal Cord Stem Cells Comments Off on Regenerative Medicine Market 2020: Analysis, Top Companies, Size, Share, Demand and Opportunity To 2025 – Eurowire | November 5th, 2020

Enhancer function, from sponges to humans

Identifying the function of enhancers, DNA regions that help to regulate gene expression and evolve rapidly, has been difficult. This area of research has been hampered by the difficultly in identifying functional conservation. Wong et al. now show that despite low sequence conservation, enhancer function is strongly conserved through the animal kingdom (see the Perspective by Harmston). Transgenic expression of sponge enhancers in zebrafish and mice demonstrates that these sequences can drive cell typespecific gene expression across species. These results suggest an unexpectedly deep level of conservation of gene regulation across the animal kingdom maintained over the course of metazoan evolution.

Science, this issue p. eaax8137; see also p. 657

In animals, gene regulatory networks specify cell identity in space and time. Transcription of genes in these networks is modulated by a class of cis-regulatory elements called enhancers that contain short (~10 base pairs) DNA sequence motifs recognized by transcription factors (TFs). In contrast to TFs, whose histories have been largely traced to the origin of the animal kingdom or earlier, the origin and evolution of enhancers have been relatively difficult to discern.

Although not a single enhancer has been shown to be conserved across the animal kingdom, enhancers may be as ancient and conserved as the TFs with which they interact. This inability to identify conserved enhancers is apparently because they evolve faster than both the TFs they interact with and the genes they regulate.

Putative enhancers in the sponge Amphimedon queenslandica had previously been identified on the basis of combinatorial patterns of histone modifications. Here, we sought to determine whether sponges share functionally conserved enhancers with bilaterians.

We primarily focused on deeply conserved metazoan microsyntenic gene pairs. These pairs are thought to be conserved because the cis-regulatory elements that regulate the developmental expression of one gene (the target gene) are located in the other gene (the bystander gene). This proposed regulatory linkage may underlie the maintenance of these microsyntenic gene pairs across 700 million years of independent evolution.

We found that enhancers present in Amphimedon microsyntenic regions drive consistent patterns of cell typespecific gene expression in zebrafish and mouse embryos. Although these sponge enhancers do not share significant sequence identity with vertebrates, they are in microsyntenic regions that are orthologous with microsyntenic regions in other metazoans and have strong histone H3 Lys4 methylation (H3K4me1) enhancer signals.

Focusing on an Islet enhancer in the Islet-Scaper microsyntenic region, we found that the sponge 709base pair enhancer, independent of its orientation, drives green fluorescent protein (GFP) expression in zebrafish cells in the hindbrain neuroepithelial region, the roof plate around the midline, the pectoral fin, and the otic vesicle; the activity overlaps with endogenous Isl2a expression. Systematic removal of sequences from the Amphimedon Islet enhancer revealed that both the 5 and 3 regions of this enhancer are required for consistent cell typespecific activity in zebrafish.

We then used the number and frequency of TF binding motifs in the Amphimedon Islet enhancer to identify putative enhancers in human, mouse, and fly Islet-Scaper regions. The candidate orthologous enhancers from humans and mice drove gene expression patterns similar to those in sponges and endogenous Islet enhancers in zebrafish.

We also demonstrated that a number of putative Amphimedon enhancers, which are outside conserved microsyntenic regions, can also drive unique expression patterns: Enhancers of sponge housekeeping genes drive broader expression patterns in zebrafish.

These results suggest the existence of an ancient and conserved, yet flexible, genomic regulatory syntax that (i) can be interpreted by the available TFs present in cells constituting disparate developmental systems and cell types, and (ii) has been repeatedly co-opted into cell typespecific networks across the animal kingdom.

This common regulatory code maintains a repertoire of conserved TF binding motifs that stabilize and preserve enhancer functionality over evolution. Once established, these enhancers may be maintained as part of conserved gene regulatory network modules over evolution. Although robust, these enhancers can evolve through the expansion and integration of new TF binding motifs and the loss of others. We posit that the expansion of TFs and enhancers may underlie the evolution of complex body plans.

Enhancers located within conserved microsyntenic units in the sponge Amphimedon queenslandica are tested in a zebrafish transgenic reporter system. In zebrafish, the sponge Islet enhancer drives a GFP reporter expression pattern similar to that of human, mouse, and zebrafish enhancers identified within the Islet-Scaper microsyntenic region. This suggests the conservation of regulatory syntax specified by flexible organizations of motifs.

Interactions of transcription factors (TFs) with DNA regulatory sequences, known as enhancers, specify cell identity during animal development. Unlike TFs, the origin and evolution of enhancers has been difficult to trace. We drove zebrafish and mouse developmental transcription using enhancers from an evolutionarily distant marine sponge. Some of these sponge enhancers are located in highly conserved microsyntenic regions, including an Islet enhancer in the Islet-Scaper region. We found that Islet enhancers in humans and mice share a suite of TF binding motifs with sponges, and that they drive gene expression patterns similar to those of sponge and endogenous Islet enhancers in zebrafish. Our results suggest the existence of an ancient and conserved, yet flexible, genomic regulatory syntax that has been repeatedly co-opted into cell typespecific gene regulatory networks across the animal kingdom.

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Deep conservation of the enhancer regulatory code in animals - Science Magazine

Spinal Cord Stem Cells Comments Off on Deep conservation of the enhancer regulatory code in animals – Science Magazine | November 5th, 2020

David Shaw walks into the hospital room and takes a seat next to the bed. He does this nearly every day, right around lunchtime.

He looks at his younger brother, Eric, tubes snaking across his arms, machines beeping and whirring. Eric does not look like Eric anymore, his skin darkened, scars deepened, features altered. They both know this but never mention it.

Eric is dying, a rare, aggressive skin cancer rampaging through his body with such ferocity that his doctors are nearly out of options. Radiation failed. Chemotherapy failed. Two bone marrow transplants failed.

As Stanford's head football coach, David Shaw is relied on to always know what to say, how to say it and when to say it; but he cannot find the words now that he and his brother are staring down what seems to be an inevitable fate.

"What do you say, where you think you've pulled at the last thread and there are no more threads?" David said. "All I could tell him was that I loved him and that I was there for him. The rest of it was really just ... I thought it was only a matter of time before he passed away."

Two years later, what happened between David and Eric remains real, present and raw -- changing their entire relationship, redefining what it means to be a brother. The words are still difficult to say, so they tip-toe around the crushing physical and mental toll Eric's cancer took on them.

David and Eric are sure to think about it all this weekend, when Stanford opens its season at Oregon on Saturday. Because the last time the Cardinal visited Eugene, neither one knew whether Eric would live or die.

After Stanford came from behind to win that game 38-31 in overtime, David delivered a message at the end of his postgame television interview, looking at the camera and saying, "To my brotherEric: I love you." He tapped the lime green pin on his black Stanford sweatshirt before he left the screen.

When Shaw became head coach at Stanford in 2011, it was the culmination of a family journey. His father was a longtime coach there; David played receiver for the Cardinal and eventually returned as an assistant under Jim Harbaugh. The entire Shaw family -- parents Willie and Gay, along with David, Eric and their sister, Tawnya -- all call the Bay Area home.

To this day, David says the day he was introduced as coach was "one of the better days in all our lives."

Yet something started to happen to Eric that no one could quite figure out. That same year, Eric found strange looking spots on his torso. His wife, Crystal, noticed the first one under his arm. Maybe it was eczema, they thought. Then the spots started to spread. He went to the doctor. They prescribed an ointment, but the spots kept popping up, until they covered his entire body. Eventually, tumors started to grow. It looked as if someone had pushed marbles under his skin. Doctors remained confounded. Eric itched uncontrollably, insatiably. His skin itched so badly, it became difficult to put on clothes, shower, sleep and go to work. He eventually needed sleep medication so he could get uninterrupted rest.

Even then, he itched subconsciously, only realizing what happened when he woke up in the morning to find his arms and sheets covered in blood. Some nights, he tried to sleep on his forearms so his body wouldn't touch the sheets, because his skin grew too sensitive to any touch. At one point, he had more than 30 open wounds on his body.

"It's something that's so pervasive and so destructive that a lot of people have mental problems -- you can't do anything without extreme pain," Eric said. "You bleed a lot through the tumors, through the lesions, through the scratching. A lot of people don't survive, really, because of the mental stress that comes with it."

Doctors had a hard time diagnosing his disease because it is often confused with psoriasis, eczema or other skin conditions. Eventually, they determined he had a rare form of skin cancer called mycosis fungoides, a type of T-cell lymphoma that affects one in 6 million people in the United States and Europe. At the time, Eric Shaw was 38.

In 2013, he and Crystal pushed for a referral to Stanford Cancer Center, which has leading experts in the disease. Mycosis fungoides is so rare, it accounts for only 4% of all non-Hodgkin lymphoma cases; among those who suffer from it, only 20% have the type of itching Eric experienced. Rarer still is to find it in people under the age of 40, and African American men often end up with the worst prognosis. All the odds were firmly against him.

"When you first hear skin cancer, your mind doesn't go too far," David said. "So initially I was like, 'There are creams and other minor surgeries. I think it'll be OK.' And then Eric said, 'No, this is not the typical skin cancer. This is inside my body. This is inside the layers of my skin, and it's not one spot. It's everywhere.'

"I didn't really get it for weeks after that because, rectifying something that I didn't think was so serious to [then thinking] ... 'Oh my gosh. So this is really cancer. This is really scary now.' It took a long time for that to sink in."

David turned it over in his mind. He was the big brother, the protector, the one who always made sure Eric would be OK. They were supposed to raise their kids together, grow old together, and reminisce about the randomness of a life spent together.

He kept coming back to one thought: You're not supposed to lose your little brother.

David and Eric Shaw grew particularly close as children as they moved from place to place when their father, Willie, took new coaching jobs. Tawnya, their older sister, fit in anywhere socially. But David and Eric, who is two years younger, stuck together.

"Like a pair," David said.

They loved riding their bikes and, when they moved to Arizona, they took advantage of the wide-open spaces in the new development where they lived. They rode for miles and miles, setting up their own ramps and doing tricks and wheelies, visiting friends along the way before returning home after dark. They played sports, too, and though David loved football as much as their dad, the basketball court is where the brothers had their epic battles.

"I was always kind of a little bit stronger and I'll never forget the last time we played one-on-one basketball," David said. "He just got better than me, and he won, and once I got over the anger and disappointment, I was proud because my younger brother had grown and was gaining confidence."

Said Eric: "I wanted nothing more than to beat him, and he wanted nothing more than to keep beating me. But, during those times, it was just us, it was me and him. He was my best friend."

David went on to play at Stanford and eventually got into coaching, against his mother's best wishes. Eric did not pursue a career in athletics. He went to San Diego State and got into a career in marketing at a financial services company, where his gregarious nature, big smile and easy laugh made him a perfect fit. Though their personalities are different -- David is stoic and introspective, Eric makes anyone feel as if they have been friends forever -- they are grounded in the same values they learned at a young age: family and faith above everything else.

Those principles only grew stronger after they found themselves in the Bay Area as adults.

After David was hired by Stanford, the entire Shaw family made it clear it would always be around to support him. Family members all have a standing invitation to come for dinner on Tuesdays. And they always attend home football games, waving and hugging David during the team's pregame walk, cheering from the stands, and then waiting for some time together once the game ends.

Even as Eric grew sick, he made it a point to go cheer for his big brother. "It's not just the football game. Our family comes together," he said. "We celebrate, we come to watch the game and cheer the team on and support David. And then afterwards, win or lose, we all wait for him to come out. It's a family day. It's been wonderful to share that experience with David."

Stanford eventually drew them even closer, and it had nothing to do with football.

Eric did not understand the gravity of his situation until his first meeting in 2013 with the doctors at Stanford Cancer Center. They put it bluntly: He had such an aggressive form of the disease that he needed immediate treatment. They would start with total skin radiation, preparing Eric to lose his hair, eyebrows, eyelashes, fingernails and toenails.

If that did not work, they would try chemotherapy next.

"All these thoughts are running through your mind," Crystal said. "'Is he going to make it? Is it going to work? What's going to happen?' At the time, our youngest daughter was 3 months old, so it was pretty overwhelming. We were just putting our lives together and then boom: you're in the middle of this cancer war."

The next week, Eric took a leave of absence from work and began four-times-a-week trips from their home east of Palo Alto, California, to Stanford Hospital, often driving as many as three hours one way in traffic. When he arrived, he went into a box and his whole body was exposed to the radiation light for about an hour. Then, he would make the drive back home to see Crystal and their four kids -- Caleb Michael, Jared Spann-Shaw, Madison Shaw and Olivia Shaw.

The radiation charred his skin. He lost weight. When he looked in the mirror, Eric no longer recognized the man looking back at him.

"Nothing prepares you for something like this," he said. "Knowing that other people were looking at me and knowing that something was very wrong, that was a daily grind to get myself up out of bed and get ready for the day, knowing that that was going to be my life."

He did this for three straight months, all to keep the disease from growing to a point where it would kill him. It worked for a short time, but the disease came back more aggressively six months later. Doctors moved on to chemotherapy treatments, some of them experimental, but also began discussing the last-resort option: a bone marrow transplant.

David and Tawnya immediately volunteered to become donors, and underwent testing. In most cases, siblings are the best chance at a donor match. Unfortunately, in their case, neither was close. On a 10-point match scale, Tawnya registered a 3, David a 5. Neither qualified to donate.

"I wanted to jump to the front of the line and say, 'Whatever I have to do, whatever you have to take out of me, however you have to do it, just do it,'" David said. "For them to come back and say that you're not a strong enough match was disheartening. It hurt me. The fact that we had to put our trust and faith in people that we didn't know, and that we're going to have to go out to registries and try to find someone who was a better match than I was, that uncertainty, and that doubt, it's hard to keep it at bay at that point. It starts to creep in."

Doctors eventually found two donors whom they believed could work, but they were not perfect matches. In early 2018, Eric and his family moved into a two-bedroom apartment near Stanford Hospital to prepare for the transplant. For three months, he went through radiation, then chemotherapy to prepare his body to accept the donor cells.

He underwent the transplant in April, feeling confident and inspired it would work. After a month, doctors did an initial check to see how many of the donor cells had survived the transplant.

None survived.

"It was like I never even had the transplant," Eric said. "That was so devastating. We just knew it was going to work. I mean, we're people of faith, and we knew everybody was praying for us, and that we were praying that this six-year journey was going to finally be over. And it wasn't over. It was crushing for them to say, 'It didn't work. We're going to have to try again.'"

The second attempt happened in September. Crystal bought lime green pins for the family to wear for lymphoma awareness. Without telling Eric or Crystal, David decided he would wear his on his shirt for the 2018 football season. In addition to that, he had lime green and yellow ribbons placed on the back of Stanford helmets as a way to show support for both cancer patients and cancer survivors.

He told his team that his brother was fighting cancer, and briefly mentioned the helmet ribbons publicly during an early-season news conference. But beyond that, David kept the severity of what was happening to his brother to himself, masking his growing nervousness, fear and anxiety as the clock ticked toward the next transplant. He had a hard time processing what was happening. He did not want to put that at the feet of his players, or his staff.

The doctors used the same donor cells that failed the first time for the second transplant on Sept. 11, 2018, because that was the only option available. But this time, doctors used even stronger drugs to prepare Eric's body to receive the donor cells -- hoping that would do enough to stop his immune system from attacking them.

When Stanford played Oregon on Sept. 22, no one in the Shaw family knew whether the transplant had worked. But the situation was more dire than the first transplant. The stronger chemotherapy caused major complications, and Eric became severely ill.

David coached the game with this in the back of his mind. Stanford rallied from a 21-7 deficit to win an overtime thriller, moving to 4-0 on the season, with a top-10 matchup against Notre Dame the following week. Back in Palo Alto, Eric watched the entire game alone in an apartment he rented near the hospital, the comeback buoying his spirits.

He had no idea his brother would speak to him through the television until he heard the words, "To my brother Eric ..."

"In that moment, I didn't feel any sickness at all," Eric said. "I can't really describe what I felt, just how proud I am of him and how awesome it made me feel that he would do that for me."

Said David: "If that transplant didn't work, I didn't know how many more games he was going to be able to see. That was an opportunity for me on national TV to speak to him, to say to my brother that against the odds, we came back and throughout the entire game, I was thinking about him."

Eric soon returned to Stanford Hospital. The chemotherapy destroyed his blood system, so he needed daily blood transfusions to stay alive. It came as no surprise when doctors told him the second transplant had failed. They had no plan now, no other donor options. David came by to visit as often as he could, but he had a hard time finding the words to say to his dying brother.

"I thought about Crystal. I thought about their kids," Shaw said. "I thought about, 'How can we help?' And then I kept going, 'We just can't get there. There has to be something else.' And we all prayed and we all comforted each other and trusted the doctors and prayed for the doctors. And just kept saying, 'Just tell us whatever options there are. Just tell us what to do and we'll do it.'"

During the day, Eric had his mother, Crystal, David, or David's wife, Kori, at his side, helping to keep his mind off what was happening to him. But in the evenings, when he was alone in his hospital room, he couldn't help but think about the dwindling medical options and his own death, slowly accepting what he believed would inevitably come.

Over seven years, everything the doctors tried had failed, and the disease always came back more aggressively. He felt exhausted in every possible way, desperate to feel better. He didn't want to die. All he wanted to do was get better, and see his kids again, hug his wife and go home. But that possibility seemed as far off as the stars.

"The doctors couldn't help us," Eric said. "They had lost all hope. There was nothing left, but we were in the deepest part of the valley, and there was nobody there but God. I said, 'You're going to take me off this Earth.' And he told me, 'Eric, you're not going to die.' That was the point at which my faith really took over, and I really had true peace."

His team of doctors huddled together again and came up with a plan many of their colleagues questioned, simply because they had never attempted it. In mid-October of 2018, they told Eric they wanted to try a third transplant.

Only this time, they wanted David to be the donor and they had only weeks to make it happen.

Eric thought, "Are they trying to kill me?"

When David was initially rejected, doctors had worked for 25 years to find a way to do half-match transplants but had virtually no success. By 2018, doctors explained that a different way to do the transplant had emerged, opening up the potential to try it with Eric. These transplants, called haploidentical transplants, typically use donor cells from a family member.

Dr. Wen-Kai Weng, Eric's bone marrow transplant physician, explained, "It was relatively new at this time. We decided to go ahead, because we knew if we didn't do it, the disease would really come back with a vengeance."

No one had ever done a third transplant with donor cells at Stanford.

"If he didn't go for this risk, he wouldn't be here," said Dr. Youn Kim, who treated Eric and heads Stanford's multidisciplinary Cutaneous Lymphoma Clinic/Program. "He wouldn't be living."

Doctors told Shaw there was a 15% chance he would not survive the transplant itself. If he did survive it, there was only about a 30% to 40% chance the donor cells would work. Compared to much steeper survival odds with no transplant at all, the decision -- filled with multiple layers of danger -- did not feel risky at all.

They had to try.

"They might have told us what the odds were, and I honestly just pushed it out of my brain," David said. "If this is the Hail Mary, hey, we're going to drop back and throw it as far as we can and send prayers along with it and hope that it works."

Without hesitation, David said to his brother, "Tell me what I need to do."

Stanford gathered in its team hotel early on Oct. 27 to begin final preparations before hosting Washington State later that day. David checked in for a 9 a.m. meeting and when it finished, he checked out of the hotel without saying a word. He walked toward the back exit, careful to make sure no one saw him, and snuck out the door to a waiting car.

Shaw sat in the passenger seat, headed toward campus and Stanford Hospital, praying all the while that what he was about to do would work.

He arrived at the hospital and was hooked up to an IV for the first dose of medication. This would not be the more traditional bone marrow transplant, where cells are extracted with a needle through the hips. Rather, the medication flowing through the IV would stimulate his body to overproduce the stem cells needed for the transplant, flooding his blood with them. The cells would then be extracted from his blood, and transplanted into Eric.

Doctors told him to expect to start feeling joint pain and tiredness within 24 hours. Those symptoms would grow only stronger over the coming days, when he came in for more medication. They told him he should stay off his feet, rest and remain hydrated.

That would be nice, David thought. But he had a game to coach. Only two people inside the program knew he had gone that morning: assistant athletic director for football operations Callie Dale, who drove him to the hospital, and defensive coordinator Lance Anderson.

"The way that I do my job, I work really hard not to make it about me," David said. "Although I wanted my team to know what my family was going through, college football is about the student-athletes. I wanted them to focus on what they needed to do. I didn't want to pull from that. I didn't want to, all of a sudden, now make it about me and my family."

A few hours later, he returned to the team hotel and acted as if he had been there the entire day, speaking nothing about his trip to the hospital. Shaw put on his lime green pin and made his way toward the bus. The short ride to the stadium felt long that day. His mind wandered before returning to the flip card in front of him.

As he exited the bus and finished the walk to the stadium, his two young nieces ran up to him. They squeezed him, holding on longer than usual, as if they knew their Uncle David was their only option, too.

He worried players would notice him moving around so slowly. If they did, no one said a word. Shaw kept pushing the pain aside, shoving his emotions down deep, saying prayers every chance he got.

On Wednesday, Shaw woke up and was so lethargic, he felt as if he was moving like a sloth. He went to the hospital for the final procedure: extracting the cells from his blood. Shaw wore comfortable clothes, arranged his pillows and settled in for a long day ahead. Doctors hooked him up to a machine that would do the work through two IVs: One took his blood so the needed donor cells could be siphoned out; the other IV would put the blood back in his body.

Eric rested on another floor in the same hospital.

David worked on his game plan, watched a few movies and occasionally stared at his own blood in the IVs, willing it to save his brother. He kept saying to himself over and over again, "God, I hope this works."

After eight hours, he was finished. Shaw then went out to practice.

"I remember walking up to him and just asking him, 'How are you doing, how are you feeling?'" Anderson said. "I could see it in him that he wasn't his normal self. He paused for a little bit and then he's like, 'I'm OK. A little bit tired, but I'm OK.' You know, just trying to put the most positive light that he could on it."

The next day, Nov. 1, 2018, Shaw went back to the hospital. It was transplant day, and he had to be with Eric to witness what they hoped would be a miracle. David and Crystal watched as Eric received a transfusion of David's stem cells, a shimmering light pink fluid flowing into his body. They sang and prayed. Already, they had received one small bit of good news: Doctors extracted 28 million cells from David's blood, about 20 million more than what they had hoped to get.

Stanford traveled the following day to Seattle, for a game against Washington. David felt guilty for leaving, but he knew there was nothing else he could do. Eric struggled in the hospital, not only from the transplant, but from the heavy chemo and radiation doctors used to prepare his body for the new cells.

Eric ran a fever of 105 degrees and vomited for days. The pain grew so intense he was put on a morphine drip and was in and out of consciousness. In Seattle, Shaw remembers being locked into the game, "except for those little moments where my heart was with my brother."

Stanford lost another heartbreaker, 27-23.

"I know us losing had nothing to do with everything David was going through," Dale said. "But just piling that on with everything else he was dealing with, it was a lot for him. He brought that up many times, about how Eric would tell him the biggest excitement for him every week was watching us play and watching us win. I know David had a lot of pressure on himself, amongst the pressure he already has as a head coach, to win for Eric. And I know that every time he did, he really felt like it was for him. And when we came up short, I know he was probably even harder on himself than he normally would have been."

Back at Stanford, David visited Eric when he could. But the waiting game took an increasing mental toll. David prides himself on his ability to compartmentalize, to focus on the only thing in front of him. He never spaces out, and he rarely gets emotional. But Shaw was falling apart on the inside.

He often found himself staring at cut-ups of red zone plays, not realizing the film had been paused for 20 minutes while his mind drifted off. Whenever that happened, he would stop and call someone, either his brother, his wife, his mother or Crystal just to see how they were doing.

"There were times where I thought life was slow motion, but it was actually moving and I was the one who was in slow motion," David said. "I found myself sometimes saying, 'Is this real? Is this really happening? This shouldn't happen.'"

In the middle of every single meeting, in the middle of every single film session, he silently prayed, "God help my brother. Just please let this one work."

"I look back now and I know more of everything that was going on and the situation," Anderson said. "I realized how much he was dealing with and how much he had to bear that week. And it's amazing that he was able to go through that week without really letting any of us really know exactly what he was going through and what a big deal this really was."

Within a few weeks, Eric started to turn a corner. Though they did not know whether the transplant had worked just yet, he showed enough improvement to leave the hospital after 52 days. David arrived for the big day, and Eric slowly put on a protective mask before shuffling to a waiting wheelchair. Doctors, nurses and support staff lined the hallway, clapping and cheering.

David cries when recalling that moment, his pent-up emotions flooding out as he describes it publicly for the first time.

"This is my little brother, after years of cancer, getting to leave the hospital," Shaw said, his voice quavering. He pauses to wipe tears from his eyes. "The nurses were crying. The doctors were crying. Because a few months earlier, they were preparing us for him to die. And he got to go home."

Three days later, doctors met with Eric and Crystal to deliver the results from the transplant. After only 27 days, Eric had none of his own blood coursing through his body.

It was all David's.

Eric picked up the phone.

"Dave," Eric said. "You have a twin. We're truly blood brothers."

Eric, who turns 46 on Friday, has lived a fairly normal life since he was declared cancer free on Jan. 1, 2019, although the coronavirus pandemic has limited how often the Shaw family can see each other.

In September, they decided to get together to celebrate all of their recent birthdays at David's house. They stayed outdoors, socially distanced, with masks on. Eric and David allowed themselves a hug, their heads turned to the side.

"Every time I see him, I just smile, you know? Because he gets to be here," David said.

Link:
'We're truly blood brothers': Stanford coach David Shaw and his recent fight to save his brother, Eric - KGO-TV

Bone Marrow Stem Cells Comments Off on ‘We’re truly blood brothers’: Stanford coach David Shaw and his recent fight to save his brother, Eric – KGO-TV | November 5th, 2020

The ' Stem Cell Banking market' research report now available with Market Study Report, LLC, is a compilation of pivotal insights pertaining to market size, competitive spectrum, geographical outlook, contender share, and consumption trends of this industry. The report also highlights the key drivers and challenges influencing the revenue graph of this vertical along with strategies adopted by distinguished players to enhance their footprints in the Stem Cell Banking market.

The latest research report on the Stem Cell Banking market assesses the major factors influencing industry growth with respect to the competitive dynamics and geographical reach. It also ensembles the challenges prevalent in this industry vertical and identifies opportunities that will further aid business expansion. Further, the report revisits all areas of the business to cover the impact of COVID-19 pandemic so as to assist stakeholders in devising new strategies and reinforcing their position in the market.

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Key pointers from COVID-19 impact analysis:

Important inclusions in the Stem Cell Banking market report:

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Latest Study explores the Stem Cell Banking Market Witness Highest Growth in nea - GroundAlerts.com

Bone Marrow Stem Cells Comments Off on Latest Study explores the Stem Cell Banking Market Witness Highest Growth in nea – GroundAlerts.com | November 5th, 2020

MUSC Hollings Cancer Center researchers identified that blocking an alternative energy pathway for T-cells after hematopoietic stem cell transplant helps reduce graft-versus-host disease (GVHD) in an animal model of leukemia.

Xue-Zhong Yu, M.D., who also is associate director of Basic Science at Hollings, and collaborators at the Indiana University School of Medicine discovered that donor T-cells must have the key enzyme lysosomal acid lipase in order to induce GVHD.

The Yu laboratory focuses on understanding the biological balance between GVHD and graft-versus-leukemia effect. Hematopoietic stem cell transplantation is used as a treatment option for some leukemia patients. T-cells in stem cell grafts from a donor are given to a leukemia patient in order to kill the cancer and reboot the patient's immune system. GVHD is a big clinical challenge because the donor T-cells, which come from the bone marrow, can attack the patient's organs. Anywhere from 30% to 70% of patients develop acute GVHD after allogeneic bone marrow transplant and 15% die.

"When we deal with hematopoietic cell transplant, it is an important balance - blocking GVHD while still allowing T-cells to do their job and control the cancer," Yu said.

Each cell in our body has its own metabolic process. Cells convert the food that is eaten into energy in order to perform their intended functions. However, cellular metabolism is often altered in various diseases. Yu researches T-cell metabolism in order to understand the balance between graft-versus-host and graft-versus-leukemia responses.

Most cells in our body require oxygen to create energy efficiently. However, this research focused on lipid, or fat, metabolism. T-cells have special metabolic processes: Sometimes they multiply so rapidly that they need an extra source of energy from free fatty acids.

Lysosomal acid lipase is an enzyme that breaks the large lipids and cholesterol into individual free fatty acid building blocks. If that enzyme is missing, there are not enough free fatty acids for energy production. This changes the T-cell metabolism, which in turn changes T-cell function.

Clinically, broad spectrum immunosuppression drugs (steroids and rapamycin) are still used as the first line of care in patients with severe GVHD. However, Yu and collaborators hypothesized that changing T-cell metabolism could reduce GVHD after hematopoietic stem cell transplantation.

"We know that the gut is the primary organ affected by GVHD. Since the gut has less oxygen, the T-cells rely on free fatty acids and must use lysosomal acid lipase. We thought if we could remove or block the activity of that, we could reduce GVHD in the gut."

The Yu Laboratory collaborated with the Indiana University School of Medicine and used a lysosomal acid lipase-deficient mouse model. T-cells lacking lysosomal acid lipase were given to mice with leukemia. As a control, T-cells with lysosomal acid lipase from normal mice were given to another group of leukemia mice. Strikingly, the mice that received the T-cells without lysosomal acid lipase did not get severe GVHD. Additionally, the T-cells from the donor lysosomal acid lipase-deficient bone marrow still killed the leukemia cells.

To increase the clinical translational potential of the work, orlistat, the FDA-approved lysosomal acid lipase inhibitor was also tested in the leukemia model. Mice with leukemia were treated with orlistat every other day after receiving bone marrow from normal mouse donors. Similar to the first experiment with the lysosomal acid lipase-deficient bone marrow, blocking the activity of lysosomal acid lipase with orlistat greatly reduced GVHD while the graft-versus-leukemia effect was preserved.

Additionally, the researchers discovered that inhibiting the lysosomal acid lipase enzyme with orlistat reduced the number of pathogenic T-cells and increased the number of regulatory T-cells. The pathogenic T-cells are the ones that cause GVHD. Regulatory T-cells are one of the "braking mechanisms" of the immune system. They help to reduce the activity of the pathogenic T-cells and prevent GVHD damage.

Therefore, blocking lysosomal acid lipase activity with orlistat preferentially stopped the donor T-cells from damaging the gut but allowed the T-cells to function during circulation and kill the leukemia cells.

The researchers' future plan is to look deeper at the biological mechanisms. For example, it is not clear how the loss or inhibition of lysosomal acid lipase affects the other metabolites in T-cells. To move this finding closer to the clinic, Yu explained that human cells can be used in a special mouse model that recreates the human immune environment.

"Looking at the immune cells in the gut was technically challenging. However, the results were exciting because our hypothesis was validated. These results encourage us to continue studying this in order to provide better treatment options to patients."

Read the original post:
Blocking energy pathway reduces GVHD while retaining anti-cancer effects of T-cells - Science Codex

Bone Marrow Stem Cells Comments Off on Blocking energy pathway reduces GVHD while retaining anti-cancer effects of T-cells – Science Codex | November 5th, 2020

Taipei, Nov. 5 (CNA) An Indonesian migrant worker who received a stem cell transplant in Taiwan in June thanked the nation on Thursday for expediting her treatment by lifting travel restrictions for her family amid COVID-19 thereby facilitating the operation that saved her life.

At a press conference that day to celebrate being discharged from the hospital, 23-year-old Nina Herlina thanked Taiwan for giving her a new lease of life and said her treatment was a testament to Taiwan's healthcare capabilities. In November last year, Nina began suffering from bouts of menorrhagia that lasted for about 20 days and came with symptoms that included dizziness, tiredness, and fever.

In February, she turned to the Taiwan International Workers' Association (TIWA), a local NGO that promotes migrant workers' rights when she was fired, shortly after a doctor diagnosed her as suffering from aplastic anemia, an autoimmune disease in which the bone marrow stops making new blood cells. With the help of the TIWA, the young woman was allowed to remain in Taiwan, where she had worked as a caregiver since October 2018.

In March, she was confirmed as having severe aplastic anemia, requiring an allogeneic stem cell transplant to treat the disease, according to the TIWA. However, at that time the COVID-19 pandemic was worsening and Nina's family were in rural Indonesia and local medical institutions lacked the technology and techniques to identify a donor in time for a bone marrow transplant.

At that time she was being kept alive in Taiwan by weekly blood transfusions. However, frequent blood transfusions can have a detrimental effect on the success of a transplant.

In addition, she also had leukopenia, a condition when a person has a reduced number of white blood cells, which increases the risk of infection. As a result, doctors at Taipei Veterans General Hospital (TVGH) determined the patient was in urgent need of a transplant, according to TIWA.

With the assistance of TIWA, a TVGH medical team explained the condition to Herlina and her family members in Indonesia via video calls. Doctors said the healthy cells for the transplant should ideally come from a family member, making her two younger sisters, aged 5 and 14, the best candidates for the operation, TIWA said.

Based on humanitarian considerations, the Central Epidemic Command Center decided in June to lift travel restrictions for her mother and sisters to visit Taiwan.

After undergoing special blood tests arranged by TVGH, the 5-year-old sister was identified as a suitable donor for a transplant. The operation was carried out after the three family members completed their 21-day quarantine in Taiwan and provided two consecutive negative COVID-19 test results.

After having received medical treatment in Taiwan for nine months, Nina was discharged from the hospital Thursday, after doctors confirmed she had recovered from the life-threatening illness.

Read more here:
Critically ill Indonesian woman thanks Taiwan for saving life - Taiwan News

Bone Marrow Stem Cells Comments Off on Critically ill Indonesian woman thanks Taiwan for saving life – Taiwan News | November 5th, 2020

Several drugs that work by targeting genetic alterations in cancer cells have won recent approval from the Food and Drug Administration as treatments for patients with diffuse large B-cell lymphoma (DLBCL).

Dr. Germame Ajebo, assistant professor of medicine at Georgia Cancer Center at Augusta University, shared information on novel treatments for the disease during the recent virtual CURE Educated Patient Leukemia & Lymphoma Summit.

In his talk, Ajebo focused on drugs meant for use in disease that has recurred or become resistant to previous treatments.

DLBCL is a usually aggressive form of the blood cancer known as a B-cell non-Hodgkin lymphoma, which affects the immune system. The disease causes rapid growth of tumors in the lymph nodes, spleen, liver, bone marrow or other organs.

Approved by the FDA within the last two years to treat aggressive DLBCL are oral Xpovio (selinexor), Polivy (polatuzumab vedotin-piiq) and Monjuvi (tafasitamab-cxix). In addition, an immunotherapy, the chimeric antigen receptor (CAR)-T cell therapy Yescarta (axi-cel), was approved to treat the disease in 2017, Ajebo reported.

Read more: Monjuvi-Revlimid Combination Approval Fills Unmet Need for Certain Patients with DLBCL.

Xpovio is a nuclear export inhibitor, which prevents cancerous cells from pushing tumor-suppressing proteins out of their nuclei. This results in tumor suppressors accumulating in the nucleus, where they can work to kill the cell.

In the phase 2b clinical trial that led to its approval which administered Xpovio by itself to 134 previously treated older adult patients the partial response rate (including those with tumor shrinkage) was 16%, the complete response rate (including those with no sign of cancer remaining) was 13% and the rate of stable disease (including patients with no progression of cancer) was 8.2%, Ajebo reported. Looking at all patients who had partial or complete responses, 38% responded for at least six months and 15% for at least 12 months.

The most common side effects that were serious or worse were low blood counts, Ajebo summarized. Other serious side effects included nausea, vomiting, diarrhea, weight loss, dizziness and infections.

Polivy is an antibody-drug conjugate that uses a targeted drug to deliver a potent chemotherapy directly to cancer cells.

It was approved based on the results of a phase 2 study of 80 previously treated patients who were divided into equally sized groups to receive the chemotherapy Treanda (bendamustine) and the targeted drug Rituxan (rituximab) with or without Polivy every 21 days for six cycles. At the end of treatment, 40% of those receiving the triplet combination had experienced a complete response, compared with 18% of those receiving Treanda and Rituxan alone. In the 63% of patients who achieved a best overall response at any point in the study while receiving the drug triplet, 48% had a response that lasted at least 12 months and 64% responded for at least six months, Ajebo noted.

Major side effects, he said, included tingling or weakness in the extremities, low blood counts, liver toxicity and tumor lysis syndrome, a condition that can damage organs due to blood chemistry issues arising from the quick destruction of tumor cells. The most common side effects of any severity included low blood counts, fatigue, diarrhea and fever.

Monjuvi, a targeted drug that inhibits the activity of the DLBCL-fueling protein CD19, was approved based on results of the phase 2 L-MIND study that demonstrated a 43% complete response rate and an 18% partial response rate in 80 previously treated adult patients who were prescribed the drug along with the targeted medication Revlimid (lenalidomide), with a median duration of response of 21.7 months. The drug is approved in combination with Revlimid for patients with recurrent or resistant DLBCL who are not eligible for, or did not agree to undergo, bone marrow transplant using their own stem cells, Ajebo said.

Serious side effects occurred in 52% of patients, he said, and included low blood counts and infections. The drug caused fatal reactions in 5% of patients, including stroke, respiratory failure, progressive multifocal leukoencephalopathy (a virus that infects the brain) and sudden death.

For more news on cancer updates, research and education, dont forget tosubscribe to CUREs newsletters here.

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Novel Targeted Drugs are Changing the Treatment of Diffuse Large B-Cell Lymphoma - Curetoday.com

Bone Marrow Stem Cells Comments Off on Novel Targeted Drugs are Changing the Treatment of Diffuse Large B-Cell Lymphoma – Curetoday.com | November 5th, 2020

Of late, there has been an increasing awareness regarding the therapeutic potential of stem cells for management of diseases which is boosting the growth of the stem cell therapy market. The development of advanced genome based cell analysis techniques, identification of new stem cell lines, increasing investments in research and development as well as infrastructure development for the processing and banking of stem cell are encouraging the growth of the global stem cell therapy market.

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One of the key factors boosting the growth of this market is the limitations of traditional organ transplantation such as the risk of infection, rejection, and immunosuppression risk. Another drawback of conventional organ transplantation is that doctors have to depend on organ donors completely. All these issues can be eliminated, by the application of stem cell therapy. Another factor which is helping the growth in this market is the growing pipeline and development of drugs for emerging applications. Increased research studies aiming to widen the scope of stem cell will also fuel the growth of the market. Scientists are constantly engaged in trying to find out novel methods for creating human stem cells in response to the growing demand for stem cell production to be used for disease management.

It is estimated that the dermatology application will contribute significantly the growth of the global stem cell therapy market. This is because stem cell therapy can help decrease the after effects of general treatments for burns such as infections, scars, and adhesion. The increasing number of patients suffering from diabetes and growing cases of trauma surgery will fuel the adoption of stem cell therapy in the dermatology segment.

Global Stem Cell Therapy Market: Overview

Also called regenerative medicine, stem cell therapy encourages the reparative response of damaged, diseased, or dysfunctional tissue via the use of stem cells and their derivatives. Replacing the practice of organ transplantations, stem cell therapies have eliminated the dependence on availability of donors. Bone marrow transplant is perhaps the most commonly employed stem cell therapy.

Osteoarthritis, cerebral palsy, heart failure, multiple sclerosis and even hearing loss could be treated using stem cell therapies. Doctors have successfully performed stem cell transplants that significantly aid patients fight cancers such as leukemia and other blood-related diseases.

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Global Stem Cell Therapy Market: Key Trends

The key factors influencing the growth of the global stem cell therapy market are increasing funds in the development of new stem lines, the advent of advanced genomic procedures used in stem cell analysis, and greater emphasis on human embryonic stem cells. As the traditional organ transplantations are associated with limitations such as infection, rejection, and immunosuppression along with high reliance on organ donors, the demand for stem cell therapy is likely to soar. The growing deployment of stem cells in the treatment of wounds and damaged skin, scarring, and grafts is another prominent catalyst of the market.

On the contrary, inadequate infrastructural facilities coupled with ethical issues related to embryonic stem cells might impede the growth of the market. However, the ongoing research for the manipulation of stem cells from cord blood cells, bone marrow, and skin for the treatment of ailments including cardiovascular and diabetes will open up new doors for the advancement of the market.

Global Stem Cell Therapy Market: Market Potential

A number of new studies, research projects, and development of novel therapies have come forth in the global market for stem cell therapy. Several of these treatments are in the pipeline, while many others have received approvals by regulatory bodies.

In March 2017, Belgian biotech company TiGenix announced that its cardiac stem cell therapy, AlloCSC-01 has successfully reached its phase I/II with positive results. Subsequently, it has been approved by the U.S. FDA. If this therapy is well- received by the market, nearly 1.9 million AMI patients could be treated through this stem cell therapy.

Another significant development is the granting of a patent to Israel-based Kadimastem Ltd. for its novel stem-cell based technology to be used in the treatment of multiple sclerosis (MS) and other similar conditions of the nervous system. The companys technology used for producing supporting cells in the central nervous system, taken from human stem cells such as myelin-producing cells is also covered in the patent.

Global Stem Cell Therapy Market: Regional Outlook

The global market for stem cell therapy can be segmented into Asia Pacific, North America, Latin America, Europe, and the Middle East and Africa. North America emerged as the leading regional market, triggered by the rising incidence of chronic health conditions and government support. Europe also displays significant growth potential, as the benefits of this therapy are increasingly acknowledged.

Asia Pacific is slated for maximum growth, thanks to the massive patient pool, bulk of investments in stem cell therapy projects, and the increasing recognition of growth opportunities in countries such as China, Japan, and India by the leading market players.

Global Stem Cell Therapy Market: Competitive Analysis

Several firms are adopting strategies such as mergers and acquisitions, collaborations, and partnerships, apart from product development with a view to attain a strong foothold in the global market for stem cell therapy.

Some of the major companies operating in the global market for stem cell therapy are RTI Surgical, Inc., MEDIPOST Co., Ltd., Osiris Therapeutics, Inc., NuVasive, Inc., Pharmicell Co., Ltd., Anterogen Co., Ltd., JCR Pharmaceuticals Co., Ltd., and Holostem Terapie Avanzate S.r.l.

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Stem Cell Therapy Market to Surge at a Robust Pace in Terms of Revenue Over2017 2025 - Royal Sutton News

Cardiac Stem Cells Comments Off on Stem Cell Therapy Market to Surge at a Robust Pace in Terms of Revenue Over2017 2025 – Royal Sutton News | November 5th, 2020

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Nov 5, 2020--

bluebird bio, Inc. (Nasdaq: BLUE) announced today that data from its gene and cell therapy programs for sickle cell disease (SCD), transfusion-dependent beta-thalassemia (TDT) and multiple myeloma (MM) will be presented, including seven oral presentations, at the 62 nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually from December 5-8, 2020.

Updated results from patients in Group C of the companys Phase 1/2 HGB-206 study of LentiGlobin for SCD gene therapy (bb1111) will be presented.

bluebird bio will also present updated long-term efficacy and safety results from the LTF-303 follow-up study; outcomes across genotypes; and outcomes in pediatric patients from Phase 3 studies HGB-207 and HGB-212 of betibeglogene autotemcel (beti-cel; formerly LentiGlobin for -thalassemia) in TDT.

Data from across the companys multiple myeloma program will be presented. Presentations will include updated safety and efficacy results from the Phase 1 CRB-401 clinical study of idecabtagene vicleucel (ide-cel, bb2121) and preliminary data from the ongoing Phase 1 CRB-402 clinical study of bb21217, as well as subgroup analyses of the pivotal Phase 2 KarMMa study of ide-cel. Ide-cel and bb21217 are investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immune therapies being studied, in partnership with Bristol-Myers Squibb, for the treatment of adult patients with MM.

Sickle Cell Disease Data at ASH

Improvements in Health-Related Quality of Life for Patients Treated with LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy

Presenting Author: Julie Kanter, MD, University of Alabama at Birmingham, Birmingham, AL

Date/Time: Oral #365, Sunday, December 6, 2020, 9:45 am PST

Resolution of Serious Vaso-occlusive Pain Crises and Reduction in Patient-Reported Pain Intensity: Results from the Ongoing Phase 1/2 HGB-206 Group C Study of LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy

Presenting Author: Alexis A. Thompson, MD, Hematology Section Head, Ann & Robert H. Lurie Childrens Hospital, Chicago, IL

Date/Time: Oral #677, Monday, December 7, 2020, 1:30 pm PST

The GRNDaD Registry: Contemporary Natural History data and an analysis of real-world patterns of use and limitations of Disease Modifying Therapy in adults with SCD

Presenting Author: Alexandra Boye-Doe, MD, University of North Carolina School of Medicine, Chapel Hill, NC

Date/Time: Poster #1730, Sunday, December 6, 2020, 7:00 am 3:30 pm PST

Transfusion-Dependent -Thalassemia Data at ASH

Long-Term Efficacy and Safety of Betibeglogene Autotemcel Gene Therapy for the Treatment of Transfusion-Dependent -Thalassemia: Results in Patients with up to 6 Years of Follow-up

Presenting Author: Janet L. Kwiatkowski, MD, MSCE, Director, Thalassemia Center at Children's Hospital of Philadelphia, Philadelphia, PA

Date/Time: Oral #153, Saturday, December 5, 2020, 12:00 pm PST

Favorable Outcomes in Pediatric Patients in the Phase 3 HGB-207 (Northstar-2) and HGB-212 (Northstar-3) Studies of betibeglogene autotemcel Gene Therapy for the Treatment of Transfusion-dependent -thalassemia

Presenting Author: Alexis A. Thompson, MD, MPH, Hematology Section Head, Ann & Robert H. Lurie Childrens Hospital of Chicago, Chicago, IL

Date/Time: Oral #154, Saturday, December 5, 2020, 12:15 pm PST

Improvement in Erythropoiesis Following Treatment with Betibeglogene Autotemcel Gene Therapy in Patients with Transfusion-Dependent -Thalassemia in the Phase 3 HGB-207 Study

Presenting Author: John B. Porter, MA, MD, FRCP, FRCPath, Head of Red Cell Unit, University College London Hospital, London, UK

Date/Time: Poster #776, Saturday, December 5, 2020, 7:00 am 3:30 pm PST

Response of patients with transfusion-dependent -thalassemia (TDT) to betibeglogene autotemcel (beti-cel; LentiGlobin for -thalassemia) gene therapy based on HBB genotype and disease genetic modifiers

Presenting Author: Mark C. Walters MD, Medical Director, Jordan Family Center for BMT & Cellular Therapies Research, UCSF Benioff Childrens Hospital Oakland, Oakland, CA

Date/Time: Poster #1699, Sunday, December 6, 2020, 7:00 am 3:30 pm PST

Multiple Myeloma Data at ASH

Updated results from the Phase I CRB-402 study of anti-BCMA CAR-T cell therapy bb21217 in patients with relapsed and refractory myeloma: correlation of expansion and duration of response with T cell phenotypes

Presenting Author: Melissa Alsina, MD, Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

Date/Time: Oral #130, Saturday, December 5, 2020, 9:45 am PST

Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in patients with relapsed and refractory multiple myeloma: updated results from phase 1 CRB-401 study

Presenting Author: Yi Lin, MD, PhD, Division of Hematology, Mayo Clinic, Rochester, MN

Date/Time: Oral #131, Saturday, December 5, 2020, 10:00 am PST

Secondary Quality-of-Life Domains in Patients With Relapsed and Refractory Multiple Myeloma Treated With the BCMA-Directed CAR T Cell Therapy Idecabtagene Vicleucel (ide-cel; bb2121): Results from the KarMMa Clinical Trial

Author: Nina Shah, MD, University of California San Francisco, San Francisco, CA

Date/Time: Oral #437, Sunday, December 6, 2020, 12:15 pm PST

Efficacy and Safety of Idecabtagene Vicleucel (ide-cel, bb2121) in Elderly Patients with Relapsed/Refractory Multiple Myeloma: KarMMa Subgroup Analysis

Presenting Author: Jess Berdeja, MD, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN

Date/Time: Poster #1367, Saturday, December 5, 2020, 7:00 am 3:30 pm PST

Characterization of Cytokine Release Syndrome in the KarMMa Study of Idecabtagene Vicleucel (ide-cel, bb2121) For Relapsed and Refractory Multiple Myeloma

Presenting Author: Ankit Kansagra, MD, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX

Date/Time: Poster #1378, Saturday, December 5, 2020, 7:00 am 3:30 pm PST

Molecular and Phenotypic Profiling of Drug Product and Post-infusion Samples from CRB-402, an Ongoing: Phase I Clinical Study of bb21217 a BCMA-directed CAR T Cell Therapy

Presenting Author: Olivia Finney, PhD, Associate Director, Immunotherapy, bluebird bio

Date/Time: Poster #1401, Saturday, December 5, 2020, 7:00 am 3:30 pm PST

Effects of Prior Alkylating Therapies on Preinfusion Patient Characteristics and Starting Material for CAR T Cell Product Manufacturing in Late-Line Multiple Myeloma

Presenting Author: Julie Rytlewski, PhD, Bristol Myers Squibb, Princeton, NJ

Date/Time: Poster #1405, Saturday, December 5, 2020, 7:00 am 3:30 pm PST

KarMMa-4: Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Targeted CAR T Cell Therapy, in High-Risk Newly Diagnosed Multiple Myeloma

Presenting Author: Saad Z. Usmani, MD, Director, Clinical Research in Hematologic Malignancies, Levine Cancer Institute/Atrium Health, Charlotte, NC

Date/Time: Poster #1418, Saturday, December 5, 2020, 7:00 am 3:30 pm PST

Healthcare Resource Utilization and Cost of Cytokine Release Syndrome and Neurologic Events in Patients with Relapsed and Refractory Multiple Myeloma Receiving the BCMA-directed CAR T Cell Therapy Idecabtagene Vicleucel (ide-cel, bb2121) in the KarMMa Trial

Presenting Author: Parmeswaran Hari, MD, Medical College of Wisconsin, Milwaukee, WI

Date/Time: Poster #1598, Saturday, December 5, 2020, 7:00 am 3:30 pm PST

A Matching-Adjusted Indirect Comparison of Efficacy Outcomes for Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-directed CAR T Cell Therapy Versus Conventional Care in Triple-Class Exposed Relapsed and Refractory Multiple Myeloma

Presenting Author: Nina Shah, MD, University of California San Francisco, San Francisco, CA

Date/Time: Poster #1653, Saturday, December 5, 2020, 7:00 am 3:30 pm PST

Idecabtagene Vicleucel (ide-cel, bb2121) Responses Are Characterized by Early and Temporally Consistent Activation and Expansion of CAR T Cells With a T Effector Phenotype

Presenting Author: Nathan Martin, PhD, Bristol Myers Squibb, Princeton, NJ

Date/Time: Poster #2315, Sunday, December 6, 2020, 7:00 am 3:30 pm PST

KarMMa-3: A Phase 3 Study of Idecabtagene Vicleucel (ide-cel,bb2121), a BCMA-Targeted CAR T Cell Therapy Versus Standard Regimens in Relapsed and Refractory Multiple Myeloma

Presenting Author: Michel Delforge, MD, PhD, University Hospital Leuven, Leuven, Belgium

Date/Time: Poster #2323, Sunday, December 6, 2020, 7:00 am 3:30 pm PST

Idecabtagene Vicleucel (ide-cel, bb2121) in Relapsed and Refractory Multiple Myeloma: Analyses of High-Risk Subgroups in the KarMMa Study

Presenting Author: Noopur S. Raje, MD, Massachusetts General Hospital, Boston, MA

Date/Time: Poster #3234, Monday, December 7, 2020, 7:00 am 3:00 pm PST

Health State Utility Valuation in Patients with Triple-Class Exposed Relapsed and Refractory Multiple Myeloma Treated with the BCMAdirected CAR T Cell Therapy, Idecabtagene Vicleucel (idecel, bb2121): Results from the KarMMa Trial

Presenting Author: Michel Delforge, MD, PhD, University Hospital Leuven, Leuven, Belgium

Date/Time: Poster #3465, Monday, December 7, 2020, 7:00 am 3:00pm PST

Abstracts outlining bluebird bios accepted data at ASH are available on the ASH conference website.

About LentiGlobin for SCD (bb1111)

SCD is a serious, progressive and debilitating genetic disease caused by a mutation in the -globin gene that leads to the production of abnormal sickle hemoglobin (HbS), causing red blood cells (RBCs) to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and painful vaso-occlusive events (VOEs). For adults and children living with SCD, this means unpredictable episodes of excruciating pain due to vaso-occlusion as well as other acute complicationssuch as acute chest syndrome (ACS), stroke, and infections, which can contribute to early mortality in these patients.

LentiGlobin for SCD (bb1111) is an investigational gene therapy being studied as a potential treatment for SCD. bluebird bios clinical development program for LentiGlobin for SCD includes the ongoing Phase 1/2 HGB-206 study and the ongoing Phase 3 HGB-210 study.

LentiGlobin for SCD was designed to add functional copies of a modified form of the -globin gene ( A-T87Q -globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). Once patients have the A-T87Q -globin gene, their red blood cells can produce anti-sickling hemoglobin (Hb A-T87Q ) that decreases the proportion of HbS, with the goal of reducing sickled red blood cells, hemolysis and other complications.

As of March 3, 2020, a total of 37 patients have been treated with LentiGlobin for SCD to-date in the HGB-205 (n=3) and HGB-206 (n=34) clinical studies. The HGB-206 total includes: Group A (n=7), B (n=2) and C (n=25).

LentiGlobin for SCD received orphan medicinal product designation from the European Commission for the treatment of SCD, and Priority Medicines (PRIME) eligibility by the European Medicines Agency (EMA) in September 2020.

The U.S. Food and Drug Administration (FDA) granted orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation for LentiGlobin for SCD. LentiGlobin for SCD continues to be evaluated in the ongoing Phase 1/2 HGB-206 and Phase 3 HGB-210 studies.

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for SCD. For more information visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT02633943 for LTF-303.

LentiGlobin for SCD is investigational and has not been approved in any geography.

About betibeglogene autotemcel

Transfusion dependent beta-thalassemia (TDT) is a severe genetic disease caused by mutations in the -globin gene that result in reduced or significantly reduced hemoglobin (Hb). In order to survive, people with TDT require chronic blood transfusions to maintain adequate Hb levels. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.

Betibeglogene autotemcel (beti-cel) adds functional copies of a modified form of the -globin gene ( A-T87Q -globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). Once a patient has the A-T87Q -globin gene, they have the potential to produce HbA -T87Q, which is gene therapy-derived adult hemoglobin, at levels that may eliminate or significantly reduce the need for transfusions.

The European Commission granted conditional marketing authorization (CMA) for beti-cel, marketed as ZYNTEGLO gene therapy, for patients 12 years and older with transfusion-dependent -thalassemia (TDT) who do not have a 0 / 0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor is not available.

As of March 3, 2020, a total of 60 pediatric, adolescent and adult patients, including 11 patients with at least 5 years of follow-up, across genotypes of TDT have been treated with beti-cel in the Phase 1/2 Northstar (HGB-204) and HGB-205 studies, and the Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies. In studies of beti-cel, patients were assessed for transfusion independence, defined as no longer needing red blood cell transfusions for at least 12 months while maintaining a weighted average Hb of at least 9 g/dL.

Non-serious adverse events (AEs) observed during clinical studies that were attributed to beti-cel included abdominal pain, thrombocytopenia, leukopenia, neutropenia, hot flush, dyspnoea, pain in extremity, tachycardia and non-cardiac chest pain. One serious adverse event (SAE) of thrombocytopenia was considered possibly related to beti-cel.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease. On April 28, 2020, the European Medicines Agency (EMA) renewed the CMA for beti-cel. The CMA for beti-cel is valid in the 27 member states of the EU as well as UK, Iceland, Liechtenstein and Norway. For details, please see the Summary of Product Characteristics (SmPC).

The U.S. FDA granted beti-cel orphan drug designation and Breakthrough Therapy designation for the treatment of TDT. Beti-cel is not approved in the United States. Beti-cel continues to be evaluated in the ongoing Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies.

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of beti-cel.

About idecabtagene vicleucel (ide-cel, bb2121)

Ide-cel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T cell immunotherapy. The ide-cel CAR is comprised of a murine extracellular single-chain variable fragment (scFv) specific for recognizing BCMA, attached to a human CD8 hinge and transmembrane domain fused to the T cell cytoplasmic signaling domains of CD137 4-1BB and CD3- chain, in tandem. Ide-cel recognizes and binds to BCMA on the surface of multiple myeloma cells leading to CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.

Ide-cel is being developed as part of a Co-Development, Co-Promotion and Profit Share Agreement between Bristol Myers Squibb and bluebird bio. Ide-cel was granted accelerated assessment by the European Medicines Agency (EMA) on March 26, 2020, and the Marketing Authorization Application (MAA) was validated by the EMA on May 20, 2020. The FDA accepted the ide-cel Biologics License Application (BLA) for priority review on September 22, 2020.

KarMMa (NCT03361748) is a pivotal, open-label, single-arm, multicenter, multinational, Phase 2 study evaluating the efficacy and safety of ide-cel in adults with RRMM in North America and Europe. The primary endpoint of the study is overall response rate as assessed by an independent review committee (IRC) according to the International Myeloma Working Group (IMWG) criteria. Complete response rate is a key secondary endpoint. Other secondary endpoints include time to response, duration of response, progression-free survival, overall survival, minimal residual disease evaluated by Next-Generation Sequencing (NGS) assay and safety. The study enrolled 140 patients, of whom 128 received ide-cel across the target dose levels of 150-450 x 10 6 CAR+ T cells after receiving lymphodepleting chemotherapy. All enrolled patients had received at least three prior treatment regimens, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and were refractory to their last regimen, defined as progression during or within 60 days of their last therapy.

CRB-401 (NCT02658929) is an open-label Phase 1 study evaluating the preliminary safety and efficacy of ide-cel in patients with relapsed and refractory multiple myeloma (RRMM). The primary endpoint of the study is safety. CRB-401 was designed as a two-part (dose escalation and dose expansion) study to determine the maximum tolerated dose and further evaluate the safety, tolerability and clinical activity at the recommended Phase 2 dose; these findings established the recommended dose of the Phase 2 KarMMa trial. All patients have been treated in the study and follow-up is ongoing.

In addition to the pivotal KarMMa and CRB-401 trials, bluebird bio and Bristol Myers Squibbs broad clinical development program for ide-cel includes clinical studies (KarMMa-2, KarMMa-3, KarMMa-4) exploring ide-cel combinations and activity in earlier lines of treatment for patients with multiple myeloma, including newly diagnosed multiple myeloma. For more information visit clinicaltrials.gov.

Ide-cel is not approved for any indication in any geography.

About bb21217

bb21217 is an investigational BCMA-targeted CAR T cell therapy that uses the ide-cel CAR molecule and is cultured with the PI3 kinase inhibitor (bb007) to enrich for T cells displaying a memory-like phenotype with the intention to increase the in vivo persistence of CAR T cells. bb21217 is being studied for patients with multiple myeloma in partnership with Bristol Myers Squibb.

bluebird bios clinical development program for bb21217 includes the ongoing Phase 1 CRB-402 study. CRB-402 is the first-in-human study of bb21217 in patients with relapsed and refractory multiple myeloma (RRMM), designed to assess safety, pharmacokinetics, efficacy and duration of effect. CRB-402 is a two-part (dose escalation and dose expansion), open-label, multi-site Phase 1 study of bb21217 in adults with RRMM. For more information visit: clinicaltrials.gov using identifier NCT03274219.

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bluebird bio to Present Data from Gene and Cell Therapy Programs During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition -...

Cardiac Stem Cells Comments Off on bluebird bio to Present Data from Gene and Cell Therapy Programs During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition -… | November 5th, 2020

This article was originally published here

Stem Cell Res. 2020 Oct 15;49:102030. doi: 10.1016/j.scr.2020.102030. Online ahead of print.

ABSTRACT

Multiple myeloma (MM) is a hematological cancer characterized by an uncontrolled proliferation of antibody-secreting plasma cells within the bone marrow. Currently, cell therapy such as chimeric antigen receptor T-cell (CAR-T) based on induced pluripotent stem cells (iPSCs) has received attention for treating MM. However, the generation of iPSCs from MM patients appears to be very rarely reported. Here we generated an iPSC line from CD34+ bone marrow cells of a patient with MM using human placenta-derived cell conditioned medium (hPCCM), offering a relatively high efficiency in humanized conditions. This iPSC line might be a useful model for research on MM.

PMID:33142253 | DOI:10.1016/j.scr.2020.102030

Read more:
Generation of normal induced pluripotent stem cell line KUMCi002-A from bone marrow CD34+ cells of patient with multiple myeloma disease having 13q...

Bone Marrow Stem Cells Comments Off on Generation of normal induced pluripotent stem cell line KUMCi002-A from bone marrow CD34+ cells of patient with multiple myeloma disease having 13q… | November 5th, 2020

Development of limited, chronic graft-vs-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (HSCT) was associated with a survival benefit for patients with high-risk myelodysplastic syndrome (MDS), according to results of a retrospective study published in Clinical Cancer Research.1

MDS is a heterogeneous group of clonal hematopoietic stem cell disorders characterized by an inadequate production of normal, mature blood cells in bone marrow.

At the present time, the only curative treatment for patients with MDS is allogeneic HSCT. Although risks associated with this approach include posttransplant relapse, as well as the development of acute and/or chronic GVHD, previous findings from studies of patients with acute leukemia treated with allogeneic HSCT have shown potent graft-vs-tumor effects manifesting as lower mortality in those patients who subsequently experienced chronic GVHD.

The clinical data used in this study were collected from more than 300 HSCT centers throughout Japan by the Japanese Data Center for Hematopoietic Cell Transplantation.

MDS was characterized as low- or high-risk disease according to the

French-American-British or World Health Organization classification schemes, depending on the year of diagnosis.2,3 Consensus criteria were used to assign GVHD severity and distinguish acute and chronic forms of the condition.

Study inclusion criteria dictated patients should be aged 16 through 70 years, had received first allogeneic HSCT between 2001 and 2017, had achieved neutrophil engraftment, and had a follow-up period of over 60 days.

Of the 3119 patients included in this study, 1193 and 1926 were classified as having low- and high-risk disease, respectively. In the overall group, the median patient age was 54 years, more than 90% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, and 85% were diagnosed with de novo disease.

At a median follow-up of 55 months, rates of 5-year overall survival (OS) were 63% and 48% for those with low- and high-risk disease, respectively (P <.001). The cumulative incidence of posttransplantation relapse at 5 years was approximately twice as high for those with high-risk disease (29%) compared with those with low-risk disease (15%; P <.001), although the cumulative incidence of nonrelapse mortality was similar in the 2 groups: 25% (low-risk disease) and 27% (high-risk disease; P =.338).

Multivariate analyses accounting for all confounding variables performed to evaluate these transplant outcomes in patient subgroups defined according to disease risk, as well the severity of GVHD and whether it was classified as acute or chronic, revealed the following:

In summarizing the results of this study, the study authors emphasized that these data demonstrated a survival benet of the graft-versus-MDS effect is present only in high-risk MDS patients with limited chronic GVHD.1

Authors of an accompanying editorial noted that in recent years, the mutational spectrum in MDS has become more associated with clinical phenotype and prognosis, and selection of a patient with MDS for HSCT has begun to incorporate the mutational landscape of the patients disease. Thus, one will have to be cautious in extrapolating the current data to ongoing and future trials, which have begun to incorporate molecular information.4

References

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Survival Benefit of GVHD in MDS Is Limited to Specific Patient Subgroup - Cancer Therapy Advisor

Bone Marrow Stem Cells Comments Off on Survival Benefit of GVHD in MDS Is Limited to Specific Patient Subgroup – Cancer Therapy Advisor | November 5th, 2020