A new phase 1/2 study has found encouraging activity from the triplet combination of azacitidine, venetoclax, and pevonedistat for patients with myelodysplastic syndromes (MDS) after failure of hypomethylating treatments.
The study, published in the Journal of Hematological Oncology, also observed benefits for patients with acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML).
“Given the established clinical activity of azacitidine plus venetoclax as well as the preclinical and clinical data supporting the use of pevonedistat in myeloid malignancies, we designed a phase 1/2 study to evaluate the triplet combination of azacitidine, venetoclax and pevonedistat in patients with newly diagnosed secondary AML who are unfit for intensive chemotherapy and in patients with MDS or CMML after failure of hypomethylating agents,” the authors wrote.
The research team conducted a phase 1/2 study to assess the combination of azacitidine, venetoclax, and pevonedistat in 40 older adult patients with MDS, AML, or CMML after failure of hypomethylating agents at a single center in Texas between March 2019 and September 2021. Eight patients were in the MDS/CMML cohort. All patients received up to 24 28-day cycles of therapy with the triple regimen.
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The primary endpoint of the phase 1 part of the study was dose-limiting toxicity of the regimen, and for phase 2, it was the composite rate of complete remission, marrow complete remission, partial remission, and hematologic improvement.
The results of the MDS/CMML cohort showed an overall response rate of 75% and a median overall survival of 10.9 months. Initial activity of the triple regimen was encouraging but the study was stopped due to poor results of a related study on azacitidine and pevonedistat combined.
The authors concluded that the triple regimen did show encouraging activity in this patient group, but the small numbers of patients and negative results from associated studies limit the ability to draw firm conclusions.
Short NJ, Muftuoglu M, Ong F, et al. A phase 1/2 study of azacitidine, venetoclax and pevonedistat in newly diagnosed secondary AML and in MDS or CMML after failure of hypomethylating agents. J Hematol Oncol. Published online July 8, 2023. doi.10.1186/s13045-023-01476-8