Abstract
FLT3, IDH1 and IDH2 inhibitors as well as venetoclax in combination with hypomethylating agents or low-dose cytarabine have expanded treatment options for patients with acute myeloid leukemia (AML). However, little data exist on the efficacy of venetoclax-based therapies in AML patients previously treated with FLT3 or IDH1/2 inhibitors. In this multicenter, retrospective cohort study, we included 44 patients who received venetoclax-based therapy after FLT3, IDH1 or IDH2 inhibitors. The overall response rate (ORR; composite of complete remission [CR]/CR with incomplete count recovery, partial remission, and morphologic leukemia free state) was 56.8% (18.2% CR) and a median overall survival of 9.2 months. While 6 out of 7 patients with IDH1 mutations who had previously been treated with ivosidenib responded to venetoclax-based therapy, FLT3-ITD mutations were associated with a lower response rate. Our data suggest that venetoclax can be an effective salvage therapy in patients previously treated with IDH1/2 or FLT3 inhibitors.
Acknowledgements
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Author contributions
J.P.B., R.M.S., B.J.B., and M.S. collected data, conceptualized the study, and wrote the initial draft of manuscript. A.D. performed statistical analyses. All authors interpreted data and contribute to subsequent manuscript drafts.
Disclosure statement
R.M.S. participated in advisory boards, and/or had a consultancy with and received honoraria from Bristol Myers Squibb and Gilead Sciences, Inc; divested equity interest in Curis Oncology. A.D.G. received research funding from Celularity, ADC Therapeutics, Aprea, AROG, Pfizer, Prelude, and Trillium; received research funding from and served as a consultant for Aptose and Daiichi Sankyo; served as a consultant and member of advisory committees for Astellas, Celgene, and Genentech; received research funding from, served as a consultant for, and was a member of advisory committees for AbbVie; and received honoraria from Dava Oncology. A.M.Z. received research funding (institutional) from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene/Cardiff oncology, Incyte, Takeda, Novartis, Aprea, and ADC Therapeutics. A.M.Z. participated in advisory boards, and/or had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Taiho, Seattle Genetics, BeyondSpring, Cardiff Oncology, Takeda, Ionis, Amgen, Janssen, Epizyme, Syndax, Gilead, Kura, Chiesi, ALX Oncology, BioCryst, and Tyme. A.M.Z. served on clinical trial committees for Novartis, Abbvie, Geron and Celgene/BMS. A.M.Z. received travel support for meetings from Pfizer, Novartis, and Cardiff Oncology. E.M.S. received research funding from Bayer; was a consultant for Amgen, AbbVie, Seattle Genetics, and Biotheryx; served as a consultant and received research funding from Syndax; was a member of the Board of Directors or advisory committee for PTC Therapeutics and Syros; served as a consultant and was member of the Board of Directors or advisory committee for Astellas Pharmaceutical, Agios Pharmaceuticals, and Genentech; served as a consultant, received research funding, and was a member of the Board of Directors or advisory committee for Daiichi-Sankyo, Celgene Pharmaceuticals, and Novartis; and is a current equity holder in privately held Auron Therapeutics. G.M. received research funding from Merck, served on the scientific board for BMS, and Abbvie, and participated as a speaker for Abbvie. A.S. served on the speakers bureau for Amgen. D.J.D. had a consultancy with Abbvie
Amgen, Autolus, Blueprint, Forty-Seven, Glycomimetrics, Inctye, Jazz, Kite, Novartis, Pfizer, Servier, and Takeda. D.J.D. received grant/research funding Abbvie, Novartis, Blueprint, Glycomimetrics. R.M.S. received personal fees from Abbvie, Actinium, Agios, Astellas, Biolinerx, Celgene, Daiichi-Sankyo, Elevate, Gemoab, Janssen, Jazz, Macrogenics, Novartis, OncoNova, Syndax, Syntrix, Syros, Takeda, Trovagene, BerGenBio, Foghorn Therapeutics, GlaxoSmith Kline, Aprea, Innate, Amgen, BMS, Boston Pharmaceuticals, Kura Oncology, and Epizyme. R.M.S. received grant funding from Abbvie, Agios, Arog, and Novartis. IA serves on advisory boards for Amgen, Kite pharmaceuticals, AbbVie, JAZZ and Agios Pharmaceuticals, and is a consultant for Pfizer, Autolus Therapeutics and Amgen, and received research support by MacroGenics and Abbvie. B.J.B. served on the advisory board for Oncovalent. MS is a member of the advisory board for Novartis and is consulting for Curis Oncology, Haymarket Media and Boston Consulting.
Data availability statement
Original data can be requested from the corresponding author.