Post-remission measurable residual disease directs treatment choice and improves outcomes for patients with intermediate-risk acute myeloid leukemia in CR1

Abstract

Objectives This study retrospectively investigated in which cycle measurable residual disease (MRD) is associated with prognosis in patients in first complete remission (CR1) of intermediate-risk acute myeloid leukemia (AML). Methods The study enrolled 235 younger patients with intermediate-risk AML. MRD was evaluated by multiparameter flow cytometry after the 1st, 2nd, and 3rd chemotherapy cycles (MRD1–3, respectively). Results No significant association was detected after the 1st and 2nd cycles. However, the 5-year incidence of relapse was higher in the MRD3-positive group (n = 99) than in the negative group (n = 136) (48.7% vs. 13.7%, P = 0.005), while 5-year disease-free survival (DFS) and overall survival (OS) were lower in the MRD3-positive group than in the negative group (43.2% vs. 81.0% and 45.4% vs. 84.1%; P = 0.003 and 0.005, respectively). Allogeneic hematopoietic stem cell transplantation led to a lower 5-year relapse, and higher DFS and OS rates than chemotherapy in the MRD3-positive group (22.3% vs. 71.5%, 65.9% vs. 23.0%, and 67.1% vs. 23.9%; P < 0.001, 0.002, and 0.022, respectively), but did not affect the MRD-negative group. Conclusions MRD3 could serve as an indicator for post-remission treatment choice and help improve outcomes for intermediate-risk AML in CR1.

Measurable Residual Disease Detection in Acute Myeloid Leukemia: Current Challenges and Future Directions

“…Their results showed no difference in relapse rates in intermediate risk patients between the group that received alloSCT and those who did not, while patients without alloSCT experienced significantly less treatment toxicity [ 102 ]. The same outcome for intermediate risk patients was observed in a recent study by Han et al [ 103 ]. The approach to omit alloSCT in MRD-negative, intermediate risk AML patients is currently prospectively tested in a pragmatic randomized trial led by members of the ELN–DAVID AML MRD Working Group.…”

“…After alloSCT, CH-associated mutations such as DNMT3A , TET2 , or ASXL1 have to be considered as highly suspicious for relapse or disease persistence [ 15 , 79 ]. Further recommendations for the implementation of MRD in clinical practice include the use of myeloablative conditioning regimens before alloSCT for MRD-positive patients [ 111 , 112 ], as well as considering consolidation chemotherapy over alloSCT for MRD-negative intermediate-risk patients [ 102 , 103 ]. In contrast, NPM1 -mutated patients with positive MRD after two induction cycles should receive alloSCT irrespective of their initial ELN risk to improve their outcome [ 118 ].…”