Faculty, Staff and Student Publications

Language

English

Publication Date

3-13-2025

Journal

Blood

DOI

10.1182/blood.2024025464

PMID

39652823

PMCID

PMC11923426

PubMedCentral® Posted Date

12-11-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Outcomes are poor in patients with higher-risk myelodysplastic syndromes (HR MDS) and frontline treatment options are limited. This phase 1b study investigated safety and efficacy of venetoclax, a selective B-cell lymphoma 2 inhibitor, at the recommended phase 2 dose (RP2D; 400 mg for 14 days per 28-day cycle), in combination with azacitidine (75 mg/m2 for 7 days per 28-day cycle) for treatment-naive HR MDS. Safety was the primary outcome, and complete remission (CR) rate was the primary efficacy outcome. Secondary outcomes included rates of modified overall response (mOR), hematologic improvement (HI), overall survival (OS), and time to next treatment (TTNT). As of May 2023, 107 patients received venetoclax and azacitidine combination at the RP2D. Best response of CR or marrow CR was observed in 29.9% and 50.5% (mOR, 80.4%), respectively. Median OS was 26.0 months, with 1- and 2-year survival estimates of 71.2% and 51.3%, respectively. Among 59 patients with baseline red blood cell and/or platelet transfusion-dependence, 24 (40.7%) achieved transfusion independence on study, including 11 (18.6%) in CR. Fifty-one (49.0%) of 104 evaluable patients achieved HI. Median TTNT excluding transplantation was 13.4 months. Adverse events reflected known safety profiles for venetoclax and azacitidine, including constipation (53.3%), nausea (49.5%), neutropenia (48.6%), thrombocytopenia (44.9%), febrile neutropenia (42.1%), and diarrhea (41.1%). Overall, venetoclax plus azacitidine at the RP2D was well tolerated and had favorable outcomes. A phase 3 study (NCT04401748) is ongoing to confirm survival benefit of this combination.

Keywords

Humans, Myelodysplastic Syndromes, Male, Azacitidine, Female, Aged, Sulfonamides, Bridged Bicyclo Compounds, Heterocyclic, Middle Aged, Antineoplastic Combined Chemotherapy Protocols, Aged, 80 and over, Adult, Treatment Outcome

Comments

This trial was registered at www.clinicaltrials.gov as #NCT02942290.

Published Open-Access

yes

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