Impact of measurable residual disease clearance kinetics in patients with AML undergoing intensive chemotherapy

The prognostic impact of measurable residual disease (MRD) in acute myeloid leukemia (AML) is unequivocal; however, the optimal time point for achieving undetectable MRD is unclear. We retrospectively studied patients with newly diagnosed (ND) AML who achieved remission with frontline intensive chemotherapy and had MRD assessed by flow cytometry after induction (time point 1 [TP1]) and after cycles 2 or 3 (TP2). Cases were grouped into MRD negative (Neg)/Neg, positive (Pos)/Neg, or Pos/Pos at TP1 and TP2, respectively. Of 1980 patients with ND AML, 277 met the inclusion criteria and were included in this analysis. The median relapse-free survival (RFS) was 73 months, 22 months, and 5 months for the MRD Neg/Neg, Pos/Neg, and Pos/Pos groups, respectively (P < .01). There was a significant difference between the Neg/Neg and Pos/Neg groups (P = .05), suggesting benefit to early MRD negativity. The median overall survival (OS) was 81 months, 40 months, and 9 months, respectively (P < .01), but the difference between Neg/Neg and Pos/Neg was not statistically significant (P = .19). Landmark analysis demonstrated the benefit of stem cell transplant (SCT), particularly in Neg/Neg intermediate-risk AML (median RFS, not reached vs 15 months; P < .01). On multivariable analysis, MRD Pos/Neg was independently associated with a worse RFS than Neg/Neg (hazard ratio, 1.73; 95% confidence interval, 1.09-2.75; P = .02) but not for OS (P = .15). In conclusion, undetectable flow MRD after induction is associated with better RFS than undetectable MRD achieved later during consolidation. SCT benefited patients with intermediate-risk AML, regardless of MRD kinetics.