Impact of Measurable Residual Disease Clearance Kinetics in Patients with AML Undergoing Intensive Chemotherapy

• Early flow-based MRD dynamics are independently associated with RFS in patients with AML undergoing frontline therapy

• Patients with intermediate-risk AML who achieved early MRD negativity still benefit from allogeneic SCT

The prognostic impact of measurable residual disease (MRD) in acute myeloid leukemia (AML) is unequivocal; however, the optimal timepoint 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 (TP1) and after cycles 2 or 3 (TP2). Cases were grouped into MRD Neg/Neg, Pos/Neg or Pos/Pos at TP1 and TP2, respectively. Of 1980 patients with ND AML, 277 met 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 < 0.01). There was a significant difference between the Neg/Neg and Pos/Neg groups (p = 0.05), suggesting benefit to early MRD negativity. Median overall survival (OS) was 81 months, 40 months, and 9 months, respectively (p < 0.01), but the difference between Neg/Neg and Pos/Neg was not statistically significant (p = 0.19). Landmark analysis demonstrated the benefit of SCT, particularly in Neg/Neg intermediate risk AML (median RFS not reached versus 15 months, p < 0.01). On multivariable analysis, MRD Pos/Neg was independently associated with a worse RFS compared with Neg/Neg (hazard ratio 1.73 [95% CI, 1.09 - 2.75], p = 0.02) but not for OS (p = 0.15). In conclusion, undetectable flow MRD after induction is associated with better RFS compared with undetectable MRD achieved later during consolidation. SCT benefitted patients with intermediate risk AML, regardless of MRD kinetics.