Olutasidenib for mutated IDH1 acute myeloid leukemia: final five-year results from the phase 2 pivotal cohort

Fecha de publicación: 01/01/2025

Autores de IIS La Fe

Pau Montesinos Fernández

Autor

Participantes ajenos a IIS La Fe

Cortes J.
Curti A.
Fenaux P.
Jonas B.A.
Krauter J.
Récher C.
Taussig D.C.
Wang E.S.
Watts J.
Wei A.
Yee K.W.L.
Tian H.
Sheppard A.
Marzac C.
de Botton S.

Grupos

Hematología y Hemoterapia

Abstract

Background: Olutasidenib is an oral, selective inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), FDA-approved for relapsed/refractory (R/R) acute myeloid leukemia (AML) based on a registrational, phase 2, open-label, multicenter trial. Methods: Results from the pre-planned interim analysis were previously published (data cut-off [DCO]: June 2021). In this final-follow up analysis, we report an additional 2 years of efficacy and safety data (DCO: June 2023). Results: At study completion, the overall population included 153 patients (median age, 71 years); 66% had received = 2 prior treatment regimens, and 39% with a hypomethylating agent. Among the 147 efficacy-evaluable patients, 51 achieved complete remission (CR) or CR with partial hematologic recovery (CRh), resulting in a CR/CRh rate of 35% (P < 0.001; 95% CI, 27–43), with 32% of responders achieving CR. The median time to CR/CRh was 1.9 months (range, 0.9–5.6 months). Among responders, 33% achieved CR/CRh within 2–4 months and 12% required = 4 months. The overall response rate (ORR) was 48% (n = 71; 95% CI, 40–56.7). Median duration of CR/CRh was 25.3 months (95% CI, 13.5–not reached), and median overall survival (OS) was 11.5 months (95% CI, 8.3–15.5). Patients with 1–2 prior regimens had a higher CR/CRh rate (41%) and longer median OS (13 months) than those with = 3 prior regimens (CR/CRh: 24%; median OS: 8.9 months). CR/CRh rates were higher among patients with R132C (42%) and R132L/G/S mutations (33%) compared with those harboring R132H mutations (17%). Response rates decreased with increasing numbers of co-mutations. Few new adverse events (AEs) and no treatment discontinuations due to AEs occurred beyond Year 3. Conclusion: These 5-year data support the durable efficacy and manageable safety profile of olutasidenib in R/R mIDH1 AML, including heavily pretreated patients. Findings highlight the potential role of olutasidenib in earlier lines of treatment, and support sustaining therapy for at least 6 months to allow for a clinical response. Further research is warranted to optimize treatment sequencing and patient selection. Trial registration: NCT02719574. © The Author(s) 2025.

Datos de la publicación

ISSN/ISSNe:: 1756-8722, 1756-8722
Tipo:: Article
Páginas:: -
DOI:: 10.1186/s13045-025-01751-w
PubMed:: 41239466
Enlace a otro recurso:: www.scopus.com
Factor de Impacto:: 4,241 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Filiaciones

Cortes J.:: Division of Hematology and SCT, Georgia Cancer Center at Augusta University, 1410 Laney Walker Blvd., CN2222, Augusta, 30912, GA, United States
Curti A.:: Institute of Hematology “Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Fenaux P.:: Service d’Hématologie Séniors, Assistance Publique Hôpitaux de Paris, Hôpital Saint-Louis, Université Paris Cité, Paris, France
Jonas B.A.:: Division of Malignant Hematology/Cellular Therapy and Transplantation, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA, United States
Krauter J.:: Medical Clinic III, Hematology and Oncology, Braunschweig Municipal Hospital, Braunschweig, Germany
Montesinos P.:: Hospital Universitari i Politècnic La Fe, Valencia, Spain
Récher C.:: Service d’hématologie, CHU de Toulouse, Institut Universitaire du Cancer Toulouse – Oncopole, Université de Toulouse, Toulouse, France
Taussig D.C.:: Haemato-oncology Unit, Royal Marsden Hospital, Institute of Cancer Research, London, United Kingdom
Wang E.S.:: Departments of Immunology and Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
Watts J.:: University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, United States
Wei A.:: Peter MacCallum Cancer Centre, Royal Melbourne Hospital and Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Yee K.W.L.:: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, M5G 2M9, ON, Canada
Tian H.:: Rigel Pharmaceuticals, Inc, South San Francisco, CA, United States
Sheppard A.:: Rigel Pharmaceuticals, Inc, South San Francisco, CA, United States
Marzac C.:: Laboratoire d’Immunologie-Hématologie, INSERM, UMR 1287, Université Paris Saclay, Gustave Roussy, Villejuif, France
de Botton S.:: Hematologie Clinique, Faculte Paris-Saclay, Institut Gustave Roussy, Institut Gustave Roussy, Villejuif, Villejuif, France

Keywords

Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Female; Follow-Up Studies; Humans; Isocitrate Dehydrogenase; Leukemia, Myeloid, Acute; Male; Middle Aged; Mutation; Pyridines; cytarabine; dinaciclib; isocitrate dehydrogenase 1; olutasidenib; venetoclax; antineoplastic agent; IDH1 protein, human; isocitrate dehydrogenase; pyridine derivative; acute myeloid leukemia; adult; aged; allogeneic stem cell transplantation; Article; asthenia; bile duct disease; cohort analysis; constipation; convalescence; diarrhea; differentiation syndrome; drug efficacy; drug safety; drug withdrawal; dyspnea; erythropenia; fatigue; fatty liver; febrile neutropenia; female; fever; follow up; gene mutation; hematopoietic stem cell transplantation; human; hypokalemia; IDH1 gene; leukemia remission; leukopenia; liver toxicity; major clinical study; male; multicenter study (topic); multiple cycle treatment; nausea; open study; overall response rate; overall survival; phase 2 clinical trial (topic); recommend

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