AML patients with specific mutations are unlikely to achieve MRD

While mutations in NPM1, NRAS, and KIT predicted high rates of measurable residual disease (MRD) clearance after induction chemotherapy, mutations in RUNX1, SF3B1, and TP53 predicted low rates of MRD clearance. Post-transplant survival was best if MRD-negative at time of transplant. In the investigated cohort, this effect was regardless of whether additional therapy was required to convert to MRD-negative status [1].

MRD is a powerful prognostic factor in acute myeloid leukaemia (AML), including in prediction of outcomes post-allogeneic stem cell transplantation (alloSCT). In AML, relapse after intensive chemotherapy is caused by a failure to eradicate MRD. However, molecular predictors of clearance as well as persistence of MRD with intensive chemotherapy are not well described.

Dr Maximilian Stahl (Memorial Sloan Kettering Cancer Center, New York, USA) provided an integrated analysis of 233 patients who underwent induction chemotherapy with baseline next-generation sequencing (NGS) followed by serial immunophenotypic monitoring for MRD while patients received additional therapy and alloSCT.

This study demonstrated that transplanted AML patients with specific molecular mutations (RUNX1, SF3B1, and TP53) were unlikely to achieve MRD-measured complete remission (CR) or CR with incomplete recovery (CRi) after induction, consolidation, or salvage therapy. Other mutations (NPM1, IDH1, KRAS) predicted high rates of MRD negativity prior to alloSCT. Additional post-induction therapy may be advantageous for some MRD-positive patients to achieve MRD prior to alloSCT. Post-transplant overall survival (OS) was improved in patients who were MRD-negative at time of transplant, regardless of whether they required additional therapy beyond induction to achieve this state. AlloSCT was highly effective at eradicating MRD, but post-transplant MRD negativity was more durable in patients who are MRD negative pre-alloSCT.

These results suggest that development of MRD-eradicating therapies has the potential to improve post-transplant outcomes. Innovative trials are warranted for patients with adverse molecular features currently unlikely to achieve MRD negativity pre-alloSCT.

1. Stahl M, et al. Molecular Predictors and Effectiveness of Measurable Residual Disease (MRD) Eradication with Chemotherapy and Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia. 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 273.

Posted on 18 February 202122 February 2021