Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory <i>IDH1</i>-mutated AML
Stéphane de Botton, Pierre Fenaux, Karen Yee, Christian Récher, Andrew H. Wei, Pau Montesinos, David Taussig, Arnaud Pigneux, Thorsten Braun, Antonio Curti, Carolyn Grove, Brian A. Jonas, Asim Khwaja, Ollivier Legrand, Pierre Péterlin, Montserrat Arnán, William Blum, Daniela Cilloni, Devendra Hiwase, Joseph G. Jurcic, Jürgen Krauter, Xavier Thomas, Justin M. Watts, Jay Yang, Olga Polyanskaya, Julie Brevard, Jennifer Sweeney, Emma Barrett, Jörge E. Cortes
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.