MRD status rather than FLT3-ITD co-mutation is linked to the benefit of CR1-allo in NPM1-mutated AML

Treatment with an allogeneic transplant in first complete remission (CR1-allo) in NPM1-mutated acute myeloid leukaemia (AML) who were minimal residual disease (MRD)-positive in peripheral blood after induction was associated with improved overall survival, relapse-free survival and a lower cumulative incidence of relapse, regardless of FLT3-ITD co-mutations.

“According to ELN 2022 recommendations, NPM1 mutation in AML is generally considered a favourable risk parameter,” started Dr Jad Othman (Royal North Shore Hospital, Australia). However, in the case of FLT3-ITD co-mutations, the risk is intermediate, and NPM1 plus adverse karyotype is considered an adverse risk factor. As in NPM1-mutated AML, the role of allogeneic transplant in the first remission remains controversial, Dr Othman and co-investigators evaluated the effect of allogeneic transplantation in participants with NPM1-mutated AML in the first complete remission concerning MRD status, baseline characteristics, and clinical and molecular features. For this purpose, the research team used data from participants who were enrolled in the NCRI AML17 (ISRCTN55675535) and AML19 (ISRCTN78449203) studies (n=737) [1].

MRD-positive participants (determined in peripheral blood, post cycle 2, AML19) benefitted from allogeneic transplant in terms of overall survival (HR 0.39; 95% CI 0.24–0.64) whereas MRD-negative participants did not (HR 0.82; 95% CI 0.50–1.33). “There was no subgroup heterogeneity in CR1-allo benefit for MRD-positive participants,” noted Dr Othman. In contrast to overall survival, the authors reported a relapse-free survival benefit (HR 0.50; 95% CI 0.32–0.79) and improved cumulative incidence of relapse in MRD-negative participants who underwent allogeneic transplants. Finally, the results were similar in MRD-positive participants with additional FLT3-ITD mutations.

“This study did not conduct FLT3-ITD MRD assessments, which may have provided additional information for CR1-allo selection,” commented Dr Othman. “Also, the results of the current study may not be generalisable to older patients, since only 16% of the population was over 60 years of age.” Nonetheless, this study showed that molecular MRD after induction chemotherapy could identify patients with NPM1-mutated AML who may benefit from allogeneic transplant in the first remission.

1. Othman J, et al. The benefit of allogeneic transplant in 1st complete remission in NPM1 mutated AML with or without FLT3 ITD is restricted to those testing MRD positive after induction - an analysis of the UK NCRI AML17 and AML 19 studies. Abstract 425, 65^th ASH Annual Meeting, 9–12 December 2023, San Diego, CA, USA.

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Posted on 7 February 202415 February 2024