Single-center phase 1-2 study of oral decitabine plus cedazuridine and venetoclax for higher-risk MDS and CMML

Hypomethylating agents are approved for higher-risk MDS. The combination of a hypomethylating agent with venetoclax is standard of care for AML. A phase 1-2 study at MD Anderson Cancer Center (Houston, TX) evaluated the first totally oral combination of decitabine plus cedazuridine and venetoclax as first-line treatment for higher-risk MDS and CMML. In phase 1, the maximum tolerated dose was not reached, and the recommended phase 2 dose was established as oral decitabine 35 mg plus cedaruzidine 100 mg once daily for the first 5 days and venetoclax 400 mg for the first 14 days of 4-week cycles. The most common grade 3 or 4 adverse events were thrombocytopenia (85%), neutropenia (74%), and febrile neutropenia (21%). In phase 2 the overall response rate was 95% (95% CI 83-99). 49% of patients proceeded to hematopoietic stem-cell transplantation. The authors conclude that the oral combination of decitabine plus cedazuridine and venetoclax for higher-risk MDS and CMML was safe in most patients, with encouraging activity.