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

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

Eitan Kugler  1   2   3 , Inbar Cohen  1   2 , Irina Amitai  2   4 , Ron Ram  2   5 , Avraham Frisch  6   7 , Boaz Nachmias  8 , Jonathan Canaani  9 , Yakir Moshe  2   5 , Baher Krayem  6   7 , Shlomzion Aumann  8 , Israel Henig  6   7 , Vladimir Vainstein  8 , Liat Shargian  1   2 , Chezi Ganzel  10 , Moshe Yeshurun  1   2 , Itay Levi  11 , Pia Raanani  1   2 , Luiza Akria  12 , Yishai Ofran  10 , Shai Shimony  1   2   13 , Ofir Wolach  1   2
Affiliations

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

Eitan Kugler et al. Br J Haematol. 2024 Sep.

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.

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References

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