Improved survival with fludarabine‐based therapies in mixed phenotype acute leukaemia: A population‐based study using the WHO 2022 classification

Mixed phenotype acute leukaemia (MPAL) is a rare subtype of acute leukaemia possessing significant therapeutic challenges, as no standardized, evidence-based treatment regimen has been defined. In this nationwide study, we aimed to assess the effect of an acute lymphoid leukaemia (ALL)-like regimen; an acute myeloid leukaemia (AML)-like regimen; and a hybrid regimen on complete remission (CR), overall survival (OS) and event-free survival (EFS). Patients were identified through the Danish National Pathology Registry and validated according to the 2022 WHO classification. OS was estimated using the Kaplan-Meier estimator, and differences in OS were assessed with the log-rank test. Inverse probability weighting was used to balance compared groups with respect to age and calendar year. Among the 43 intensively treated WHO 2022 MPAL patients, 25 (58.1%) received ALL regimens, 10 (23.3%) received AML regimens and 8 (18.6%) received hybrid regimens. CR rates by treatment regimen were highest for hybrid regimen (87.5% (95% confidence interval (CI): 47.3%-99.7)), followed by ALL regimen (72% (95% CI: 50.6%-87.5%)) and AML regimen (40% (95% CI: 12.2%-73.8%)). Treatment with hybrid regimens consisting of a fludarabine-based approach (fludarabine, cytarabine, G-CSF and idarubicin [FLAG-IDA], fludarabine, cytarabine, G-CSF and mitoxantrone [Mito-FLAG] or fludarabine, etoposide, G-CSF, mitoxantrone and cytarabine [FLEGMA]) was associated with improved OS and EFS compared to a classic daunorubicin-cytarabine AML regimen (p = 0.02 and p = 0.002 respectively).