Abstract Topic: 4. Acute myeloid leukemia - Clinical
Background: AML is heterogeneous disease with much fewer treatment options. 7 + 3 and different high dose ARA-C combinations are still the mainstream approaches for patients that fit the intensive therapy. New treatment with AZA+ven has emerged for the elderly or unfit AML pts, but there are few publications about its efficacy as the first line treatment in youngs pts with de novo AML, especially AML with myelodysplasia related changes (MRC-AML). The question whether allo-HSCT is necessary in CR1 if MRD-negativity was achieved after the 1st induction course and sustains afterwards still remains open
Aims: To define in a randomized fashion the role of allo-HSCT in AML pts who achieved MRD-negative CR after the first 7 + 3 cycle disregard of ELN risk group (excluding MRC-AML and inv16)
Methods: In Feb 2021 Russian Leukemia study group has initiated a multicenter prospective clinical trial registered on ClinTrialGov NCT05339204. ELN 2017 and WHO 2016 classification were used for patients’ stratification. Induction and consolidation treatment was planned to be different for pts with MRC-AML (low intensive: Aza-Ven or Aza-LDIda-LDAra-C) and for all other AML types (two 7 + 3 (dauno 60m2) and two FLAG cycles, followed by 6 maintenance 5 + 5 cycles with ARA-C and 6MP). Cytogenetic and molecular testings were done and MRD was also monitored by MFC in a centralized lab. Pts with molecular markers were followed in parallel by PCR. MRC-AML pts (group C) were all candidates for early allo-HSCT (within 4 cycles). Inv16 pts (group A) were considered as candidates for allo-HSCT only if MRD persisted after the 4th cycle at high levels or was increasing. All other AML pts were included in Group B, and those who achieved MRD-negative CR after the first 7 + 3 cycle were randomized to early allo-HSCT (within 4 cycles) or no allo-HSCT (or postponed allo-HSCT in case of MRD-conversion)
Results: 104 pts from 11 Centers were enrolled from Feb 2021 to Nov 2022. 9 pts (inv16 AML) have formed Group A (8,6%), 73 – Group B (70,3%), 22 MRC-AML pts – Group C (21,1%). 84 pts were eligible for evaluation of min 2 inductions. Total CR rate was 76,2% (Group A – 100%, B – 75,4%, C – 66,7%), 60-day mortality - 10,7% (A-0%, B – 15,8%, C – 11,1%), refractory AML – 10,7% (A-0%, B – 8,8%, C – 22,2%). In group B among 48 CR pts 43 achieved CR after the 1st ind. cycle and 33 of them (76,7%) were MRD-negative. So 29 of 33 were randomized: 14 - to early allo-HSCT (7 were performed with a median time from CR to allo-HSCT 6,3 mо), 15 – to postponed allo-HSCT. All 10 pts that were MRD-positive after the 1st 7 + 3 were directed to allo-HSCT, and 5 were transplanted with a Me time 5,5 mo. All CR pts from Group C were allocated to allo-HSCT (70% were already transplanted with a Me time from CR to allo-HSCT=2,9 mo). No one was transplanted from group A, and one has a late relapse and was transplanted in 2nd CR. 1-year OS for the whole cohort of pts was 70%, DFS – 73%. It’s too early to compare randomized groups. 1-y OS for Gr. A =100%, Group B - 74%, Group C - 50%. 1-y DFS for Group A – 100%, for Gr. B - 68%, for Gr. C - 75%
Summary/Conclusion: To our knowledge our trial is the only one investigating in a randomized fashion the role of allo-HSCT in 1st CR for AML pts who are MRD-negative after the 1st induction disregard ELN 2017 risk groups.The first results of a prospective clinical trial have demonstrated that it took a long time from CR achievement to allo-HSCT in the majority of AML pts - 5,5-6,3 mo. MRC-AML pts reached allo-HSCT somewhat earlier – 2,9 mo, with 75% 1-year DFS. Further follow-up will answer the posed question
Keywords: HSCT, Acute myeloid leukemia, Minimal residual disease (MRD)