General AML

MRD in older AML patients treated with HMAs correlates with response

Hypomethylating agents (HMAs) elicit unique responses compared to other chemotherapeutics, and therefore the best way to measure response to HMA treatment is debated, with the value of Minimal Residual Disease (MRD) largely unstudied, particularly in the elderly Acute Myeloid Leukemia (AML) population.

Prajwal Boddu et al. from the University of Texas MD Anderson Cancer Center, Houston, TX, USA, retrospectively studied the prognostic value of MRD detection by multi-color flow cytometry (MFC) in a cohort of elderly AML patients treated with HMAs. The results of the study were reported in a Letter to the Editor of Leukemia on 18th September 2017.

In total, 194 newly diagnosed AML patients (age ≥ 60 years) who were treated on and off prospective clinical trials with either azacitidine, decitabine or guadecitabine between February and November in 2012 were included in this study. Overall, 116 patients had MRD analysis performed on bone marrow specimens obtained at time of assessment of response or afterwards.

Among these 116 patients, 59% achieved either morphologic complete remission (CR) or CR with incomplete recovery of platelets (CRp) or counts (CRi), and 53% (n = 61) had evaluable MRD data. MRD in evaluable patients was measured at the time of response and at 3-months post CR/CRi/CRp. At the time of response (overall evaluable patients = 55), 16 patients were MRD negative and 39 patients were MRD positive. At 3-months post CR/CRi/CRp, 25 patients were MRD negative and 36 patients were MRD positive.

Key Findings:
  • Cumulative incidence of relapse (CIR) in MRD negative and positive patients respectively
    • 2-year CIR rate at response; 43% vs 84%,  adjusted sub-hazard ratios (aSHR) = 0.24, P < 0.001
    • 2-year CIR rate at 3-months post CR/CRi/CRp; 48% vs 86%, aSHR = 0.33, P < 0.001
  • Relapse-free survival (RFS) or overall survival (OS) = no significant difference between cohorts

The authors concluded that patients achieving negative MRD at CR, or at any time within 3-months post CR, had a lower CIR and suggested that monitoring MRD after this time frame should improve and guide treatment strategy. In particular, in the elderly AML patient subset this could potentially steer therapy towards lower doses or agents that are more readily tolerated.

The study is limited by its retrospective nature and the relatively small subset, but nevertheless is an indicator that future trials with HMAs would benefit from the added value of MRD testing.

References
  1. Boddu P. et al. Achievement of a negative minimal residual disease state after hypomethylating agent therapy in older patients with AML reduces the risk of relapse. Leukemia. 2017 Sept 18. DOI: 10.1038/leu.2017.285. [Epub ahead of print].