1. Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML.
- Author
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de Botton, Stéphane, Fenaux, Pierre, Yee, Karen, Récher, Christian, Wei, Andrew, Montesinos, Pau, Taussig, David, Pigneux, Arnaud, Braun, Thorsten, Curti, Antonio, Grove, Carolyn, Khwaja, Asim, Legrand, Ollivier, Peterlin, Pierre, Arnan, Montserrat, Blum, William, Cilloni, Daniela, Hiwase, Devendra, Jurcic, Joseph, Krauter, Jürgen, Thomas, Xavier, Watts, Justin, Yang, Jay, Polyanskaya, Olga, Brevard, Julie, Sweeney, Jennifer, Barrett, Emma, Cortes, Jorge, and Jonas, Brian
- Subjects
Humans ,Adult ,Middle Aged ,Aged ,Aged ,80 and over ,Pyridines ,Quinolines ,Leukemia ,Myeloid ,Acute ,Prognosis ,Isocitrate Dehydrogenase - 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.
- Published
- 2023