Gilteritinib with or without venetoclax for relapsed/refractory FLT3‐mutated acute myeloid leukaemia

Summary Patients with FLT3 ‐mutated acute myeloid leukaemia (AML) that relapse or are refractory (R/R) to intensive induction have poor outcomes. Gilteritinib has recently become standard‐of‐care for patients with R/R FLT3 ‐mutated AML. We investigated whether adding venetoclax to gilteritinib (gilt‐ven) improves outcomes as compared with gilteritinib monotherapy. We included patients treated with gilteritinib ( n = 19) and gilt‐ven ( n = 17) for R/R AML after intensive chemotherapy. Gilteritinib and gilt‐ven groups did not differ in terms of mCRc rates (53% and 65%, p = 0.51) and realization of allogeneic haematopoietic stem‐cell transplantation (HSCT, 47% and 35%, p = 0.5). Overall survival (OS) was comparable between groups, although a trend towards better OS was seen with gilt‐ven (12‐month OS 58.8% 95% CI 39.5%–87.6%) versus gilteritinib (42.1% 95% CI 24.9%–71.3% for gilteritinib). Early salvage with gilt‐ven versus any other gilteritinib‐based approach was associated with the best outcome ( p = 0.031). Combination therapy was associated with increased haematological toxicity. In summary, gilt‐ven did not improve remissions or HSCT‐realization rates in patients with R/R FLT3 ‐mutated AML as compared with gilteritinib and was associated with increased haematological toxicity. Although OS did not differ, a trend towards better survival was suggested with gilt‐ven and a survival benefit was shown for gilt‐ven approach when sequenced early for salvage.