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

Br J Haematol. 2024 Sep;205(3):932-941. doi: 10.1111/bjh.19548. Epub 2024 May 23.

Abstract

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.

Keywords: Fms‐related receptor tyrosine kinase 3 (FLT3) mutation; acute myeloid leukaemia (AML); gilteritinib; venetoclax.

MeSH terms

  • Adult
  • Aged
  • Aniline Compounds* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic* / therapeutic use
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / mortality
  • Male
  • Middle Aged
  • Mutation*
  • Pyrazines* / administration & dosage
  • Pyrazines* / therapeutic use
  • Recurrence
  • Sulfonamides* / therapeutic use
  • fms-Like Tyrosine Kinase 3* / genetics

Substances

  • gilteritinib
  • fms-Like Tyrosine Kinase 3
  • venetoclax
  • Aniline Compounds
  • Sulfonamides
  • Bridged Bicyclo Compounds, Heterocyclic
  • Pyrazines
  • FLT3 protein, human