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
. 2023 Jul 11;7(13):3117-3127.
doi: 10.1182/bloodadvances.2022009411.

Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML

Stéphane de Botton  1 , Pierre Fenaux  2 , Karen Yee  3 , Christian Récher  4 , Andrew H Wei  5 , Pau Montesinos  6 , David C Taussig  7 , Arnaud Pigneux  8 , Thorsten Braun  9 , Antonio Curti  10 , Carolyn Grove  11 , Brian A Jonas  12 , Asim Khwaja  13 , Ollivier Legrand  14 , Pierre Peterlin  15 , Montserrat Arnan  16 , William Blum  17 , Daniela Cilloni  18 , Devendra K Hiwase  19 , Joseph G Jurcic  20 , Jürgen Krauter  21 , Xavier Thomas  22 , Justin M Watts  23 , Jay Yang  24 , Olga Polyanskaya  25 , Julie Brevard  25 , Jennifer Sweeney  25 , Emma Barrett  25 , Jorge Cortes  26
Affiliations

Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML

Stéphane de Botton et al. Blood Adv. .

Abstract

Olutasidenib (FT-2102) is a potent, selective, oral, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1). Overall, 153 IDH1 inhibitor-naive patients with mIDH1R132 relapsed/refractory (R/R) acute myeloid leukemia (AML) received olutasidenib monotherapy 150 mg twice daily in the pivotal cohort of this study. The median age of participants was 71 years (range, 32-87 years) and the median number of prior regimens received by patients was 2 (1-7). The rate of complete remission (CR) plus CR with partial hematologic recovery (CRh) was 35%, and the overall response rate was 48%. Response rates were similar in patients who had, and who had not, received prior venetoclax. With 55% of patients censored at the time of data cut-off, the median duration of CR/CRh was 25.9 months. The median duration of overall response was 11.7 months, and the median overall survival was 11.6 months. Of 86 patients who were transfusion dependent at baseline, a 56-day transfusion independence was achieved in 29 (34%), which included patients in all response groups. Grade 3 or 4 treatment-emergent adverse events (≥10%) were febrile neutropenia and anemia (n = 31; 20% each), thrombocytopenia (n = 25; 16%), and neutropenia (n = 20; 13%). Differentiation syndrome adverse events of special interest occurred in 22 (14%) patients, with 14 (9%) grade ≥3 and 1 fatal case reported. Overall, olutasidenib induced durable remissions and transfusion independence with a well-characterized and manageable side effect profile. The observed efficacy represents a therapeutic advance in this molecularly defined, poor-prognostic population of patients with mIDH1 R/R AML. This trial was registered at www.clinicaltrials.gov as #NCT02719574.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: S.d.B. has received honoraria and research funding from Forma Therapeutics; has received honoraria and research funding from and is a consultant to Agios; has received honoraria from, is a consultant to, and is on the speakers’ bureau for Celgene; has received honoraria from and is a consult to Astellas, Daiichi Sankyo, Syros, AbbVie, Bayer, and Janssen; has received honoraria from Seattle Genetics; and is a consultant to Pierre Fabre, Novartis, Pfizer, and Servier. P.F. is a consultant to and has received honoraria and research funding from AbbVie, Janssen, Jazz Pharmaceuticals, Novartis, and Bristol Myers Squibb (BMS). K.Y. is a consultant to and has received research funding from F. Hoffman-La-Roche and Jazz Pharmaceticals; is a consultant to and has received honoraria and research funding from Novartis; is a consultant to Astellas, BMS/Celgene, GlaxoSmithKline, Pfizer, Shattuck Labs, Taiho, and Takeda; has received research funding from Astex, Forma Therapeutics, Geron, Gilead, Janssen, Karyopharm, and Treadwell; and has received honoraria from AbbVie. C.R. is a consultant to, has received honoraria and research funding from, and is a board/advisory committee member for AbbVie, BMS, and Jazz Pharmaceuticals; has received honoraria and research funding from and is a board/advisory committee member for Amgen and Astellas; is a board/advisory committee member for Novartis, Pfizer, and Takeda; and is a consultant to, has received honoraria from, and is a board/advisory committee member for Servier. A.H.W. has received honoraria and research funding from, is a consultant to, is on the speakers’ bureau, and is a board/advisory committee member for Astellas; has received honoraria and research funding from, is on the speakers’ bureau, and is a board/advisory committee member for AbbVie/Genentech, Amgen, Celgene/BMS, and Novartis; has received research funding and honoraria from, is a consultant to, and is a board/advisory committee member for Servier and Syndax; has received honoraria from, is a consultant to, and is a board/advisory committee member for Janssen and Gilead; has received honoraria from and is a board/advisory committee member for MacroGenetics and Pfizer; has received honoraria and research funding from and is a board/advisory committee member for AstraZeneca; has received research funding from Astex; is an employee of the Walter and Eliza Hall Institute; and is eligible for a fraction of the royalty stream related to venetoclax. P.M. is a consultant to, has received research funding from, and is on the speakers’ bureau for AbbVie, BMS, and Pfizer; is a consultant to and has received research funding from Menarini/Stemline, Novartis, and Takeda; is a consultant to and is on the speakers’ bureau for Jazz Pharmaceuticals and Astellas; and is a consultant to Otsuka, Kura Oncology, BeiGene, Incyte, Ryvu, and Nerviano. D.C.T. has received research funding from Bayer and from AbbVie to attend the American Society of Hematology meeting. A.P. has received honoraria from and is a consultant to AbbVie; is a consultant to Gilead; and has received honoraria from Astellas, Agios, Pfizer, and Jazz Pharmaceuticals. A.C. is a board/advisory committee member for Jazz Pharmaceuticals, Pfizer, Novartis, and AbbVie. C.G. is a board/advisory committee member for Astellas, AbbVie, and Otsuka; has received honoraria for her institution for participation in advisory boards for Astellas, AbbVie, and Otsuka, and for chairing an educational meeting for AbbVie. B.A.J. has received research funding for his institution, is a consultant to, and is a board/advisory committee member for, AbbVie, BMS, Genentech/F. Hoffman-La-Roche, Jazz Pharmaceuticals, Pfizer, and Treadwell; has received research funding for his institution, is a consultant to, and is a data monitoring committee member for Gilead; has received research funding for his institution, is a consultant to, and is a protocol steering committee member for GlycoMimetics; is a consultant to and a board/advisory committee member for Rigel, Servier, Takeda, and Tolero; has received travel reimbursement/expenses from AbbVie and Rigel; has received research funding for his institution from 47, Accelerated Medical Diagnostics, Amgen, Arog, Celgene, Daiichi Sankyo, F. Hoffman-La-Roche, Forma Therapeutics, Hanmi, Immune-Onc, Incyte, Loxo Oncology, LP Therapeutics, Pharmacyclics, and Sigma Tau. P.P. is a board/advisory committee member for Jazz Pharmaceuticals, Astellas, Celgene, and AbbVie. M.A. is a consultant to and a board/advisory committee member for BMS/Celgene and Novartis; and is a consultant to Astellas, Jazz Pharmaceuticals, and Pfizer. W.B. is a board/advisory committee member for Syndax; has received research funding from Xencor and Celyad; and has received honoraria from AmerisourceBergen. D.K.H. has received research funding from Novartis. J.G.J. is a consultant to, a board/advisory committee member for, and has received research funding from AbbVie, Daiichi Sankyo, and Celgene; is a consultant to, and a board/advisory committee member for Novartis; and has received research funding from Arog Pharmaceuticals, Astellas, Forma Therapeutics, Genentech, Kura Oncology, PTC Therapeutics, and Syros Pharmaceuticals. J.M.W. has received research funding from and is a board/advisory committee member for Takeda; has received research funding from Immune System Key Ltd and Takeda; and is a board/advisory committee member for Genentech, Rafael Pharma, Reven Pharma, and Celgene/BMS. J.Y. has received research funding from Seattle Genetics, Janssen, Arog, Loxo Oncology, and Agios. O.P., J.B., J.S., and E.B. are employees of and hold stock in Forma Therapeutics. J.C. has received research funding for his institution from and is a consultant to AbbVie, BMS, Novartis, Pfizer, Takeda, Daiichi, Jazz Pharmaceuticals, Merus, and Forma Therapeutics; has received research funding for his institution from Astellas and Amphivena; and is a consultant to Gilead, BioLineRx, and BioPath. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Duration of response for patients with CR/CRh (n = 51).
Figure 2.
Figure 2.
OS. (A) OS for patients in the full analysis population (N = 153). (B) OS for patients in the efficacy-evaluable population with CR/CRh (n = 51), other responders (n = 20), and nonresponders (n = 76). Other responders are patients with CRi, PR, or MLFS. Nonresponders are patients in response assessment categories other than CR/CRh, CRi, PR, and MLFS.
Figure 3.
Figure 3.
Patients who were transfusion dependent at baseline and achieved TI for ≥56 days. Other responders are patients with CRi, PR, or MLFS. Nonresponders are patients in response assessment categories other than CR/CRh, CRi, PR, and MLFS.
See this image and copyright information in PMC

References

    1. Botton SD, Watts J, Baer M, et al. PS1051 FT-2102, an IDH1 m inhibitor, induces mutation clearance in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) treated in phase 1 dose escalation and expansion study. HemaSphere. 2019;3(s1):475–476.
    1. DiNardo CD, Ravandi F, Agresta S, et al. Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML. Am J Hematol. 2015;90(8):732–736. - PMC - PubMed
    1. Gross S, Cairns RA, Minden MD, et al. Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med. 2010;207(2):339–344. - PMC - PubMed
    1. Cairns RA, Mak TW. Oncogenic isocitrate dehydrogenase mutations: mechanisms, models, and clinical opportunities. Cancer Discov. 2013;3(7):730–741. - PubMed
    1. Losman JA, Looper RE, Koivunen P, et al. (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science. 2013;339(6127):1621–1625. - PMC - PubMed

Publication types

Associated data