<i>IDH2</i> mutation is associated with favorable outcome among older adults with newly diagnosed acute myeloid leukemia treated with hypomethylating agent-based therapy
Mutations of isocitrate dehydrogenase (IDH) are recurrent in newly diagnosed (ND) acute myeloid leukemia (AML) and the prevalence increases with age. The prognostic impact of IDH mutations in AML remains controversial. IDH inhibitors generally have a favorable side effect profile, making them an attractive option for older patients. This retrospective analysis aimed to describe the prevalence and prognostic impact of IDH mutations in a large cohort of ND AML patients aged ≥60 years enrolled in the Beat AML clinical trial. A total of 1,023 patients were included. IDH mutations were detected in 28% of the patients, including 9.7% IDH1mut, 18.9% IDH2mut, and 1.0% had a mutation in IDH1 and IDH2. IDH frequently co-occurred with DNMT3A (38%), NPM1 (35%), and SRSF2 (34%). In patients treated with intensive chemotherapy, IDH mutations were not prognostic for overall survival (OS) (p=0.76), while OS was longer for patients with IDH2mut compared to IDHwt in patients treated with hypomethylating agent (HMA)-based therapy (median OS of 18.5 vs 10.2 months, p.
Authors
- William Blum (ORCID: https://orcid.org/0000-0003-0111-7465)
- Elie Traer (ORCID: https://orcid.org/0000-0001-8844-2345)
- Wendy Stock (ORCID: https://orcid.org/0000-0002-8349-9200)
- Shivani Handa (ORCID: https://orcid.org/0000-0002-1932-6209)
- Uma Borate (ORCID: https://orcid.org/0000-0002-4958-4962)
- Vu H. Duong (ORCID: https://orcid.org/0000-0003-0278-7727)
- Martha Arellano (ORCID: https://orcid.org/0000-0003-1636-1962)
- Alice S. Mims (ORCID: https://orcid.org/0000-0002-8971-2199)
- Ross L. Levine (ORCID: https://orcid.org/0000-0002-7884-1905)
- Ying Huang (ORCID: https://orcid.org/0009-0000-3117-145X)
- Sonja Marcus
- Brian Druker (ORCID: https://orcid.org/0000-0001-8331-8206)
- Mona Stefanos
- Tara L. Lin (ORCID: https://orcid.org/0000-0002-0242-6449)
- Gary J. Schiller (ORCID: https://orcid.org/0000-0002-7508-3467)
- Molly Martycz
- Joshua F. Zeidner (ORCID: https://orcid.org/0000-0002-9014-1514)
- Olatoyosi M. Odenike (ORCID: https://orcid.org/0000-0002-4027-4124)
- Fieke W. Hoff (ORCID: https://orcid.org/0000-0002-7128-1255)
- Ashley O. Yocum
- Eytan M. Stein (ORCID: https://orcid.org/0000-0001-8992-9390)
- Rebecca L. Olin (ORCID: https://orcid.org/0000-0002-5060-0384)
- John C. Byrd (ORCID: https://orcid.org/0000-0002-8778-1000)
- Leonard Rosenberg
- Amy Burd (ORCID: https://orcid.org/0000-0002-9625-2813)
- Emily Curran (ORCID: https://orcid.org/0000-0001-8159-4733)
- Yazan F. Madanat (ORCID: https://orcid.org/0000-0001-9573-2690)
- Catherine C. Smith (ORCID: https://orcid.org/0000-0003-0160-7026)
- Rina Li Welkie (ORCID: https://orcid.org/0000-0001-9477-4581)
- Timothy F. Chen (ORCID: https://orcid.org/0000-0003-4189-8403)
- Ronan T. Swords
- Maria R. Baer
- Nyla A. Heerema
Institutions
- University of North Carolina at Chapel Hill (US)
- University of Maryland, Baltimore (US)
- Memorial Sloan Kettering Cancer Center (US)
- Emory University (US)
- University of California, Los Angeles (US)
- Oregon Health & Science University (US)
- University of California, San Francisco (US)
- University of Chicago (US)
- Southwestern Medical Center (US)
- Center for Cancer and Blood Disorders (US)
- University of Kansas Medical Center (US)
- University Cancer and Blood Center (US)
- U-M Rogel Cancer Center (US)
- UNC Lineberger Comprehensive Cancer Center
- The Ohio State University (US)
- University of Cincinnati (US)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Haematologica
- Published
- 2025-11-06
- DOI
- https://doi.org/10.3324/haematol.2025.288743
- Citations
- 1
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 1.77
Funders
- Amgen
- Pfizer
- Gilead Sciences
- Oregon Health and Science University
- Foghorn Therapeutics
- Incyte
- Syndax Pharmaceuticals
- Astellas Pharma
- Swedish Orphan Biovitrum
- MorphoSys
- Sun Pharma
- Sierra Oncology
- Genentech
- Daiichi Sankyo Europe