Real-world analysis of CPX-351 in AML-MR: A multicentre study from the MARROW consortium

CPX-351 is a standard front-line induction regimen for newly diagnosed acute myeloid leukaemia (AML) with myelodysplasia-related changes (AML-MRC). The 2022 International Consensus Classification (ICC) and World Health Organization (WHO) classifications redefine AML with myelodysplasia-related (AML-MR) to include myelodysplasia-related mutations as well as cytogenetic abnormalities. Clinical outcomes of patients treated with CPX-351 within these refined AML-MR classifications remain unclear. We conducted a retrospective, multicentre study of 235 adults with newly diagnosed AML-MR treated with CPX-351 across seven US academic centres. Patients were stratified by age (younger: <60 vs. older: ≥60 years) and AML-MR subgroup: cytogenetics (AML-MRc), molecular (AML-MRm) and antecedent haematological disorder (AML-AHD). Outcomes included complete remission (CR) and CR with incomplete recovery (CR/CRi), rates of allogeneic haematopoietic stem cell transplant (alloHSCT) and overall survival (OS). The overall CR/CRi rate of CPX-351 was 52%, with no difference by age. AML-MRm had the highest CR/CRi rate (57%). Among CR/CRi responders, 55% underwent alloHSCT (<60 years: 53% vs. ≥60 years: 57%). Median OS was 13.8 months with no significant difference by age. Younger AML-MRm patients had longer median OS compared with older AML-MRm patients (38.0 vs. 19.5 months; p = 0.05). Favourable outcomes in AML-MRm, particularly in younger patients, support molecular classification in guiding therapy and selectively extending CPX-351 use beyond older adults.