Venetoclax in combination with hypomethylating agent for the treatment of advanced myeloproliferative neoplasms and acute myeloid leukemia with extramedullary disease

Abstract

The combination of venetoclax and hypomethylating agent (HMA/venetoclax) has emerged as a treatment option for patients with de novo acute myeloid leukemia (AML) who are unfit to receive intensive chemotherapy. In this single-center retrospective study, we evaluated clinical outcomes following treatment with HMA/venetoclax in 35 patients with advanced myeloproliferative neoplasms, myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes or AML with extramedullary disease. The composite complete remission (CR) rate (including confirmed/presumed complete cytogenetic response, acute leukemia response-complete, CR and CR with incomplete hematologic recovery) was 42.9% with median overall survival (OS) of 9.7 months. Complex karyotype was associated with inferior median OS (3.7 versus 12.2 months; p = 0.0002) and composite CR rate (22% versus 50.0%; p = 0.2444). Although SRSF2 mutations were associated with higher composite CR rate (80.0% versus 28.0%; p = 0.0082), this was not associated with longer median OS (10.9 versus 8.0 months; p = 0.2269). Future studies should include these patient subgroups.

Keywords:

• Myeloproliferative neoplasm
• myelodysplastic/myeloproliferative neoplasm
• acute myeloid leukemia
• extramedullary disease
• venetoclax
• hypomethylating agents
• azacitidine
• decitabine

Author Contributions

Khaled Sanber designed the study, collected clinical and genomic data, performed statistical analysis, interpreted the data and wrote the manuscript; Kevin Ye collected clinical and genomic data, interpreted the data and wrote the manuscript; Matthew Newman collected clinical and genomic data and edited the manuscript; Hua-Ling Tsai performed the statistical analysis, interpreted the data and edited the manuscript, Jonathan A. Webster, Ivana Gojo, Gabriel Ghiaur, Gabrielle T. Prince, Lukasz P Gondek, B. Douglas Smith, Mark J. Levis, Amy E. DeZern, Alexander J. Ambinder and William Brian Dalton interpreted the data and edited the manuscript; Tania Jain designed the study, interpreted the data, wrote the manuscript and supervised the project.

Disclosure statement

Tania Jain has received institutional research support from CTI Biopharma, Syneos Health, Incyte, and has served on the advisory board for Care Dx, Bristol Myers Squibb, Incyte, Abbvie, and CTI. Amy E. DeZern previously acted as a consultant and in advisory roles for Bristol-Myers Squibb, Novartis, Geron, Gilead Sciences, Taiho. Ivana Gojo has received research funding from Merck, Amgen, Genentech, and has served on the advisory board for Immunogen, Amgen, Gilead, Bristol Myers Squibb, Clearview.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.