Among patients with high-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML), combination azacitidine plus venetoclax appears to be both safe and effective, according to research published in The Lancet Haematology.

MDS are a class of cancers defined by ineffective hematopoiesis, bone marrow dysplasia, and peripheral blood cytopenia. Among patients with these syndromes, there is a risk of transformation to leukemia, including acute myeloid leukemia.

Among patients with MDS who are not eligible for allogeneic hematopoietic stem-cell transplantation — which may lead to a cure — azacitidine is a commonly used therapeutic option. Venetoclax, a monoclonal antibody targeting anti-apoptotic protein B-cell lymphoma-2, has previously been shown to be effective in the setting of leukemia.

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Previous study has suggested, furthermore, that venetoclax may induce apoptosis in high-risk MDS cells. For this phase 1-2 study ( Identifier: NCT04160052), researchers are evaluating combination azacitidine plus venetoclax among patients with high-risk MDS or CMML. In the present Lancet paper, researchers published analyses from the phase 1 portion of the trial.

Overall, 23 patients were enrolled to the study’s phase 1 portion. Among these patients, 17 were included in a hypomethylating agent–naive cohort, while 6 were included in a hypomethylating agent–failure cohort. In the overall patient group, the median age was 68 years, 78% of patients were male sex, and 12 patients had myelodysplastic-type or myeloproliferative-type CMML.

The median follow-up was 13.2 months. At this point, the maximum tolerated study dose was not reached; the recommended phase 2 dose was azacitidine 75 mg/m2 for 5 days plus venetoclax 400 mg for 14 days. The overall response rate was 87% (95% CI, 66%-97%).

The most common grade 3 or worse treatment-related adverse events were neutropenia (39%), thrombocytopenia (39%), lung infection (30%), and febrile neutropenia (17%). There were 3 deaths from sepsis, which were determined to be not related to the study protocol.

“Ultimately, the question of whether the addition of venetoclax to azacitidine improves overall survival in patients with high-risk myelodysplastic syndromes will be answered by the ongoing phase 3, randomised, controlled trial VERONA,” the authors wrote.

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 


Bazinet A, Darbaniyan F, Jabbour E, et al. Azacitidine plus venetoclax in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: phase 1 results of a single-centre, dose-escalation, dose-expansion, phase 1-2 study. Lancet Haematol. Published online September 2, 2022. doi:10.1016/S2352-3026(22)00216-2