Venetoclax and hypomethylating agent therapy in high risk myelodysplastic syndromes: a retrospective evaluation of a real-world experience

Abstract

Treatment with hypomethylating agents (HMAs) azacitidine or decitabine is the current standard of care for high risk myelodysplastic syndromes (MDSs) but is associated with low rates of response. The limited number of treatment options for patients with high risk MDS highlights a need for new therapeutic options. Venetoclax is an inhibitor of the BCL-2 protein which, when combined with an HMA, has shown high response rates in unfit and previously untreated acute myeloid leukemia. We performed a retrospective study of high risk MDS patients receiving combination HMA plus venetoclax in order to determine their effectiveness in this context. We show that in our cohort, the combination results in high response rates but is associated with a high frequency of myelosuppression. These data highlight the efficacy of combination HMA plus venetoclax in high risk MDS, warranting further prospective evaluation in clinical trials.

Keywords:

• Myelodysplastic syndromes
• venetoclax
• hypomethylating agents

Disclosure statement

R.M. is a founder, consultant, equity holder, and serves on the Board of Directors of Forty Seven Inc. B.M. is an employee of Roche/Genentech. The remaining authors declare no competing financial interests.

Additional information

Funding

This work was supported by NIH R01-CA188055 (to RM), the Ludwig Institute for Cancer Stem Cell Research and Medicine (to RM), the Advanced Residency Training Program at Stanford (to AE), the ASH Research Training Award to Fellows (to TZ), the A.P. Giannini Foundation (to TZ), and the Stanford Cancer Institute Fellowship Award (to TZ). RM is a Leukemia & Lymphoma Society Scholar.