Older Age, STAG2, and DNMT3A Mutations Predict Superior Posttransplant Survival in Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax Plus Hypomethylating Agents.

Authors

Momna Warraich, Sudhesh Kumar, Mahnoor Fatima, Kristen McCullough, Aref Al-Kali, Hassan B Alkhateeb, Kebede H Begna, Abhishek Mangaonkar, Antoine N Saliba, Aasiya Matin, Mark R Litzow, William Hogan, Mithun V Shah, Mrinal M Patnaik, Animesh Pardanani, James Foran, Lisa Sproat, Nandita Khera, Ayalew Tefferi, Naseema Gangat

Published in

American journal of hematology. Aug 23, 2026. Epub Aug 23, 2026.

Abstract

Venetoclax (Ven) plus hypomethylating agents (HMA) is standard frontline therapy for newly diagnosed AML (ND-AML) patients unfit for intensive chemotherapy and is also considered in younger, fit patients. However, consolidation with allogeneic stem cell transplant (ASCT) is often required to secure durable remission. The current study examines posttransplant outcomes in patients with ND-AML treated with frontline Ven-HMA who subsequently underwent ASCT. A total of 111 ND-AML patients (58% male, 60% secondary/therapy-related, median age 70 years [range, 37-80]) received a median of 3 cycles of Ven-HMA. Mutations at the time of diagnosis included RUNX1 (18%), SRSF2 (17%), TP53 (16%), ASXL1, IDH2, K/NRAS, TET2 (14% each), STAG2 (11%), DNMT3A (8%). All patients were in CR/CRi at the time of transplant including 88% after Ven-HMA. Measurable residual disease (MRD) by flow cytometry was detectable in 18/76 (24%) patients. Donors were mostly HLA-matched unrelated (75%); 51% receiving fludarabine/melphalan conditioning and 67% posttransplant cyclophosphamide. At a median follow-up of 15 months, 42 (38%) of patients have died and 18 (16%) experienced posttransplant relapse. Median posttransplant survival was not reached (NR), with 1-, 2-, 3-year survival rates of 69%/60%/57%, respectively. On multivariate analysis, age ≥ 65 years, STAG2 mutation (STAG2^MUT), and DNMT3A^MUT were associated with superior posttransplant survival. Patients were stratified into low- (0-1 point), intermediate- (2 points), and high-risk (3 points); age < 65 years, STAG2 wild type, and DNMT3A wild type, with 3-year survival rates of 89%, 59%, and 19%, respectively (p < 0.01). Taken together, age, STAG2^MUT and DNMT3A^MUT stratified posttransplant survival in Ven-HMA treated patients with ND-AML.

PMID:
42633550
Bibliographic data and abstract were imported from PubMed on 23 Aug 2026.

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