Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2022 Nov:122:106942.
doi: 10.1016/j.leukres.2022.106942. Epub 2022 Aug 29.

Efficacy of FLT3 and IDH1/2 inhibitors in patients with acute myeloid leukemia previously treated with venetoclax

Jan Philipp Bewersdorf  1 , Rory M Shallis  2 , Andriy Derkach  3 , Aaron D Goldberg  1 , Anthony Stein  4 , Eytan M Stein  1 , Guido Marcucci  4 , Amer M Zeidan  2 , Shai Shimony  5 , Daniel J DeAngelo  5 , Richard M Stone  5 , Ibrahim Aldoss  4 , Brian J Ball  4 , Maximilian Stahl  6
Affiliations
Multicenter Study

Efficacy of FLT3 and IDH1/2 inhibitors in patients with acute myeloid leukemia previously treated with venetoclax

Jan Philipp Bewersdorf et al. Leuk Res. 2022 Nov.

Abstract

Small molecule inhibitors targeting mutant FLT3, IDH1, and IDH2 as well as venetoclax-based combination therapies have expanded treatment options for patients with acute myeloid leukemia (AML). As the landmark trials leading to the approval of FLT3, IDH1, and IDH2 inhibitors in R/R-AML were conducted prior to the widespread use of venetoclax, it is unclear how these results apply in the current era of venetoclax based therapy frequently being used in the frontline treatment of AML. In this multicenter, retrospective cohort study, we included 53 patients who received FLT3, IDH1 or IDH2 inhibitors after disease progression on venetoclax-based therapy. Among patients treated with targeted agents after venetoclax, the overall response rate (ORR; composite of complete remission [CR]/CR with incomplete count recovery, partial remission, and morphologic leukemia free state) was 17.7 % (n = 9 patients) and median OS of 4.2 months. Eight of 9 patients responding to targeted agents after venetoclax received gilteritinib. None of the patients with RAS pathway mutations responded to targeted agents after venetoclax. Additionally, mutations in TP53 and KRAS were associated with shorter OS among patients treated targeted agents. Our data suggest that response rates to targeted therapies after venetoclax are low and novel therapeutic strategies are warranted.

Keywords: AML; Acute myeloid leukemia; Enasidenib; Gilteritinib; Ivosidenib; Outcomes; Targeted agents; Venetoclax.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest 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.

Comment in

Publication types

MeSH terms