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

de Botton, S; Fenaux, P; Yee, K; Recher, C; Wei, AH; Montesinos, P; Taussig, DC; Pigneux, A; Braun, T; Curti, A; Grove, C; Jonas, BA; Khwaja, A; Legrand, O; Peterlin, P; Arnan, M; Blum, W; Cilloni, D; Hiwase, DK; Jurcic, JG; Krauter, J; Thomas, X; Watts, JM; Yang, J; Polyanskaya, O; Brevard, J; Sweeney, J; Barrett, E; Cortes, J

Author(s): de Botton, S; Fenaux, P; Yee, K; Recher, C; Wei, AH; Montesinos, P; Taussig, DC; Pigneux, A; Braun, T; Curti, A; Grove, C; Jonas, BA; Khwaja, A; Legrand, O; Peterlin, P; Arnan, M; Blum, W; Cilloni, D; Hiwase, DK; Jurcic, JG; Krauter, J; Thomas, X; Watts, JM; Yang, J; Polyanskaya, O; Brevard, J; Sweeney, J; Barrett, E; Cortes, J;
Details: Publication Year 2023,Volume 7,Issue #13,Page 3117-3127
Journal Title: Blood Advances
Publication Type: Research article
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.
Keywords: Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Pyridines; *Quinolines/therapeutic use; *Leukemia, Myeloid, Acute/drug therapy/genetics/chemically induced; Prognosis; Isocitrate Dehydrogenase/genetics
Department(s): Clinical Haematology
PubMed ID: 36724515
Publisher's Version: https://doi.org/10.1182/bloodadvances.2022009411
Open Access at Publisher's Site: https://doi.org/10.1182/bloodadvances.2022009411
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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Last Modified: 2024-08-20 06:57:07