Achievement of a Negative MRD State After Hypomethylating Agent Therapy in Older Patients with AML to Reduce Risk of Relapse

The presence of minimal residual disease (MRD) is associated with poorer outcomes in patients with acute myeloid leukemia (AML) treated with traditional cytarabine- and anthracycline-based regimens. Researchers sought to understand whether the same dynamic exists for patients treated with hypomethylating agents.

In this study, 116 patients with AML treated with single-agent azacytidine, decitabine, or guadecitabine had MRD analysis performed on bone marrow specimens. The median age was 76 years. Sixty-nine (59%) patients achieved complete remission (CR) or CR with incomplete recovery of platelets or blood counts. The median number of cycles to achieve response was 2 (range, 1-6). Sixty-one patients (53%) had evaluable MRD data at the time of response, of whom 25 (41%) became MRD-negative at 3 months cumulative after CR.

MRD-negative status was associated with a reduced cumulative risk of relapse (P = 0.012) but not improved relapse-free survival (RFS) or overall survival (OS). The researchers concluded that this was due to a high frequency of nonrelapse deaths attributable to comorbidities and infections in the MRD-negative group. Likewise, patients who achieved MRD-negative status at CR and at any time up to 3 months postresponse were not associated with improved RFS or OS despite a significantly lower cumulative risk of relapse (P = 0.05).

In this group of older patients with AML treated with hypomethylating agents, achieving an MRD-negative state was associated with a reduced risk of relapse but not improved RFS or OS. Further research on patients experiencing a lower rate of nonrelapse mortality may be required to assess the true impact of MRD-negative status on survival.

Boddu P, et al. ASCO Abstract 7018.

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