Outcomes for Patients with IDH -Mutated Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

Background: Disease relapse after hematopoietic cell transplantation (HCT) is a major cause of treatment failure for patients with acute myeloid leukemia (AML). Maintenance therapy following HCT for patients with targetable mutations such as mutated IDH1 or IDH2 may improve outcomes, and clinical trials evaluating this strategy are ongoing. However, current clinical outcomes of IDH1 - and IDH2 -mutated AML patients following HCT have not been well-described.  Methods: In this multicenter retrospective analysis, 112 adult patients with either IDH1 - or IDH2 -mutated AML who underwent HCT were identified at Massachusetts General Hospital, Dana Farber Cancer Institute, and Ohio State University. Mutation testing was performed using next-generation sequencing panels. Patient characteristics were collected retrospectively, and their outcomes — including progression-free survival (PFS), overall survival (OS), relapse, and non-relapse mortality — were analyzed.  Findings: The median patient age was 64·1 years. 78·5% of patients had intermediate- or adverse-risk disease by European LeukemiaNET criteria. Commonly detected co-mutations were DNMT3A (35·7%), NPM1 (33·1%), and FLT3-ITD (13·4%).  The median follow-up was 27·5 months. For IDH1- mutated patients, the 1- and 2-year PFS was 75% and 58%, respectively, and the 1- and 2-year OS was 78% and 74%, respectively. For IDH2- mutated patients, the 1- and 2-year PFS was 64% and 58%, respectively, and the 1- and 2-year OS was 75% and 68%, respectively. Interpretation: Our analysis provides important benchmarks for analysis and interpretation of results emerging from ongoing clinical trials evaluating maintenance IDH1 and IDH2 inhibitor therapy for AML patients following HCT.  Funding: This project has no funding source to report. Declaration of Interests: Dr. Eisfeld reports other from Karyopharm, personal fees from Vigeo, outside the submitted work. Dr. E Chen has nothing to disclose. Dr. Li has nothing to disclose. Dr. Luskin has nothing to disclose. Dr. Mims reports other from Jazz, other from Syndax, other from Abbvie, other from Kura oncology, personal fees from Agios, other from Novartis, outside the submitted work. Dr. Jones reports personal fees from Pharmacyclics LLC, outside the submitted work. Dr. Antin has nothing to disclose. Dr. Cutler reports other from Incyte, other from Kadmon, other from Jazz, other from Medsenic, other from Generon, other from Mesoblast, outside the submitted work. Dr. Koreth reports personal fees from Equilium, personal fees from Amgen, personal fees from Moderna Therapeutics, personal fees from Biolojic Design, personal fees from EMD Serono, other from Therakos, other from Cugene, grants from Miltenyi, grants from BMS, grants from Reneron, other from Clinigen, outside the submitted work. Dr. Gooptu has nothing to disclose. Dr. Romee has nothing to disclose. Dr. El-Jawahri has nothing to disclose. Dr. McAfee has nothing to disclose. Dr. Defilipp reports grants from Incyte, grants from Regimmune, personal fees from Syndax, outside the submitted work. Dr. Soiffer reports other from Kiadis, other from Gilead, other from Rheos, other from Cugene, other from Precision Bioscience, other from Mana Therapeutics, other from VOR Biopharma, other from Novartis, other from Juno, other from Celgene, other from Alexion, other from National Marrow Donor Program, outside the submitted work. Dr. YB Chen reports personal fees from Incyte, personal fees from Takeda, personal fees from Magenta, personal fees from Kiadis, other from Actinium, other from Equilium, other from Abbvie, outside the submitted work. Dr. Fathi reports grants from Takeda, personal fees from Boston Biomedical, personal fees from PTC Therapeutics, personal fees from Amphivena, personal fees from Astellas, personal fees from Daiichi Sankyo, personal fees from Novartis, grants and personal fees from Celgene/BMS, personal fees from Trovagene, personal fees from Forty Seven , personal fees from NewLink Genetics , personal fees from Pfizer, personal fees from Abbvie, grants and personal fees from Seattle Genetics , grants and personal fees from Agios, personal fees from Amgen, personal fees from Trillium, personal fees from Kura Oncology, personal fees from Blueprint, personal fees from Genentech, outside the submitted work. Ethics Approval Statement: This study was approved by the Institutional Review Boards at the Dana-Farber Harvard Cancer Center and Ohio State University Comprehensive Cancer Center