Regardless of the advancements made in understanding the genetic and molecular landscapes of acute myeloid leukemia (AML) in young patients, bespoke treatment approaches are yet to be adopted. Based on the NCCN 2009 guidelines,2 AML risk stratification depends on genetic/cytogenetic abnormalities of AML cells and groups patients into favorable-risk" (FR), intermediate-risk (IR) or poor-risk (PR) categories. This will then determine the treatment pathway of whether they will receive allogeneic stem cell transplantation (allo-SCT). Currently, treatment of IR patients is less defined and often post-induction treatment with allo-SCT is adopted. Nevertheless, this approach does not appropriately take into account the heterogeneity in this group regarding the risk of disease relapse. Despite high complete remission (CR) rates in these patients, overall survival (OS) remains low due to the high rate of relapse incidence.3

Adriano Venditti et al., from the Gruppo Italiano Malattie EMatologiche dellAdulto (GIMEMA) Foundation investigated in a multicenter prospective clinical trial (NCT01452646) the benefit of risk-adapted, MRD-based therapy in young adults with AML. This study consisted of the integration of pre-treatment cytogenetics/genetics with post-treatment MRD assessment (detected using multiparametric flow cytometry [MFC]) to stratify patients to receive post-consolidation autologous stem cell transplantation (auto-SCT) or allo-SCT.1

In conclusion, the authors recognized that this study has intrinsic limitations due to scientific progression over time, such as better understanding of basic biology, new AML classification and increased MRD monitoring, which makes the historical control not wholly comparable. However, this is the first study that attempts to apply a prospective program of risk-adapted, MRD-driven treatment in patients with NCCN-IR AML, that integrates genetics and post-consolidation MRD status.

Patients that were in the NCCN-IR group demonstrated that allo-SCT can be avoided if patients are tested MRD-negative after induction therapy. In contrast, if patients are MRD-positive, allo-SCT improved OS and prolonged DFS to comparable levels as those of patients in the NCCN-FR group. Patients in the IR group, who could not be monitored for LAIP had an inferior 2-year OS of 50% when compared to the other risk groups. This suggests that, in this group, a number of patients could have benefited from an allo-SCT. Further studies that integrate baseline factors and monitor MRD are needed, as it could potentially be a promising tool to refine and customize outcome prediction in patients with AML.

Link:
GIMEMA AML1310 trial of risk-adapted, MRD-guided therapy for young patients with newly diagnosed AML - AML Global Portal