Prolonged treatment-free remission after venetoclax in combination with a hypomethylating agent in acute myeloid leukemia with inv(16).
- 1Department of Medicine, Stanford Health Care, Stanford, CA, USA.
- 2Division of Hematology, Department of Medicine, Stanford Health Care, Stanford, CA, USA.
- 3Division of Hematology, Department of Medicine, Stanford Health Care, Stanford, CA, USA. [email protected].
Abstract
Core binding factor acute myeloid leukemia (CBF-AML)-defined by t(8;21) or inv(16) chromosomal rearrangements-is classified as favorable-risk disease per the European LeukemiaNet 2022 risk model and is typically treated with intensive chemotherapy. Patients unsuitable for intensive therapy increasingly receive hypomethylating agents plus venetoclax (HMA/ven), though CBF-AML was excluded from pivotal trials of this regimen. Furthermore, HMA/ven is typically administered as indefinite therapy in AML; however, there is increasing interest in exploring the feasibility of therapy cessation given persistent treatment-free remissions with this regimen. Here, we report the first case of sustained treatment-free remission following HMA/ven in CBF-AML. Features in this case that suggest a higher likelihood of achieving a durable treatment-free remission include inv(16) disease and rapid measurable residual disease (MRD) clearance. We summarize the current retrospective data comparing response rates of inv(16) vs. t(8;21) AML to HMA/ven: inv(16) AML consistently exhibits higher response rates compared with t(8;21) disease, although an overall survival benefit is not well established. Emerging data also suggest achieving MRD-negative complete remission after induction may predict more durable outcomes. This case provides proof-of-concept that carefully selected CBF-AML patients achieving sustained MRD-negative remission with HMA/ven can successfully discontinue therapy. Prospective evaluation of HMA/ven in unfit CBF-AML patients, weighed against dose-attenuated intensive chemotherapy, is needed to define its role and optimal duration.
Related
- Venetoclax plus hypomethylating agent improves response rates but not survival in TP53-mutated myelodysplastic syndromes.
- Efficacy of Sorafenib Combined with Venetoclax and Azacitidine in Newly Diagnosed FLT3-ITD-Mutant Acute Myeloid Leukemia: Remission Efficacy and Prognostic Influence of Post-Remission Consolidation Therapy
- Prolonged Active SARS-CoV-2 Infection in a Patient With Chronic Lymphocytic Leukemia on Venetoclax.
- Real‐World Survival Outcomes of Venetoclax Combination Therapies in Acute Myeloid Leukemia: Impact of Minimal Residual Disease Status and Antifungal Prophylaxis
- Combination therapy with nelarabine, pegaspargase, and venetoclax for adult patients with R/R T-cell ALL/LBL
BibTeX
@article{shannon2026prolonged,
title = {{Prolonged treatment-free remission after venetoclax in combination with a hypomethylating agent in acute myeloid leukemia with inv(16).}},
author = {Morgan L Shannon and Jared Wallace and Amy Kuo and Gabriel N Mannis},
journal = {Annals of hematology},
year = {2026},
month = aug,
doi = {10.1007/s00277-026-07237-0},
url = {https://europepmc.org/article/MED/42963459},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Prolonged treatment-free remission after venetoclax in combination with a hypomethylating agent in acute myeloid leukemia with inv(16).
AU - Morgan L Shannon
AU - Jared Wallace
AU - Amy Kuo
AU - Gabriel N Mannis
PY - 2026
DA - 2026/08/10
JO - Annals of hematology
DO - 10.1007/s00277-026-07237-0
UR - https://europepmc.org/article/MED/42963459
AB - Core binding factor acute myeloid leukemia (CBF-AML)-defined by t(8;21) or inv(16) chromosomal rearrangements-is classified as favorable-risk disease per the European LeukemiaNet 2022 risk model and is typically treated with intensive chemotherapy. Patients unsuitable for intensive therapy increasingly receive hypomethylating agents plus venetoclax (HMA/ven), though CBF-AML was excluded from pivotal trials of this regimen. Furthermore, HMA/ven is typically administered as indefinite therapy in AML; however, there is increasing interest in exploring the feasibility of therapy cessation given persistent treatment-free remissions with this regimen. Here, we report the first case of sustained treatment-free remission following HMA/ven in CBF-AML. Features in this case that suggest a higher likelihood of achieving a durable treatment-free remission include inv(16) disease and rapid measurable residual disease (MRD) clearance. We summarize the current retrospective data comparing response rates of inv(16) vs. t(8;21) AML to HMA/ven: inv(16) AML consistently exhibits higher response rates compared with t(8;21) disease, although an overall survival benefit is not well established. Emerging data also suggest achieving MRD-negative complete remission after induction may predict more durable outcomes. This case provides proof-of-concept that carefully selected CBF-AML patients achieving sustained MRD-negative remission with HMA/ven can successfully discontinue therapy. Prospective evaluation of HMA/ven in unfit CBF-AML patients, weighed against dose-attenuated intensive chemotherapy, is needed to define its role and optimal duration.
SN - 0939-5555
SN - 1432-0584
ER -