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

Autor: Stéphane de Botton, Pierre Fenaux, Karen W.L. Yee, Christian Récher, Andrew H Wei, Pau Montesinos, David C. Taussig, Arnaud Pigneux, Thorsten Braun, Antonio Curti, Carolyn S Grove, Brian A. Jonas, Asim Khwaja, Ollivier Legrand, Pierre Peterlin, Montserrat Arnan, William Blum, Daniela Cilloni, Devendra K. Hiwase, Joseph G. Jurcic, Jürgen Krauter, Xavier Thomas, Justin M Watts, Jay Yang, Olga Polyanskaya, Julie Brevard, Jennifer Sweeney, Emma Barrett, Jorge Cortes
Rok vydání: 2023
Předmět:
Zdroj: Blood Advances.
ISSN: 2473-9537
2473-9529
DOI: 10.1182/bloodadvances.2022009411
Popis: Olutasidenib (FT-2102) is a potent, selective, oral, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1). Overall, 153 IDH-1 inhibitor naïve 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. Median age (range) was 71 years (32-87) and the median number of prior regimens was 2 (1-7). The rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh) was 35% (n=51; 95% CI, 27.0-43.0) and the overall response rate was 48% (n=71; 95% CI, 40.0-56.7). 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, median duration of CR/CRh was 25.9 months (95% CI, 13.5-NE). Median duration of overall response was 11.7 months (95% CI, 6.9-25.9). Median overall survival was 11.6 months (95% CI, 8.9-15.5). Of 86 patients who were transfusion-dependent at baseline, a 56-day transfusion independence was achieved in 29 (34%), including patients in all response groups. Grade 3/4 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-prognosis patient population with mIDH1 R/R AML. This trial is registered at www.clinicaltrials.gov as NCT02719574.
Databáze: OpenAIRE
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