The U.S. Food and Drug Administration granted breakthrough-therapy designation to the BCL2 inhibitor venetoclax, in combination with cytarabine, for the treatment of older patients with treatment-naïve acute myeloid leukemia (AML) who are ineligible to receive intensive chemotherapy.
The decision was supported by data from an ongoing, open-label, phase Ib trial of venetoclax plus low-dose cytarabine in 20 older patients (>65 years). As of last follow-up (October 1, 2015), 18 patients (median age = 74 years) had received the venetoclax combination: Eight patients received venetoclax 600 mg, and 10 received venetoclax 800 mg. The median time on study was 127.5 days (range = 30-272 days).
At 12-month follow-up, the overall response rate was 44 percent (complete remission, n=4; complete remission without complete marrow recovery, n=4; resistant disease, n=8; death before evaluation, n=2).
Two patients in the venetoclax 800 mg group experienced a dose-limiting toxicity (grade 4 thrombocytopenia lasting >42 days). The most common adverse event (AE) was febrile neutropenia (33.3%). AEs occurring in ≥30 percent of patients included nausea (77.8%), anemia (55.6%), febrile neutropenia (38.9%), neutropenia (38.9%), fatigue (38.9%), vomiting (33.3%), diarrhea (33.3%), and hypokalemia (33.3%).
Sources: Roche press release, July 28, 2017; Lin T, Strickland S, Fiedler W, et al. Phase 1b/2 study of venetoclax with low-dose cytarabine in treatment-naïve patients aged ≥65 years with acute myelogenous leukemia. Abstract #E911. Presented at the European Hematology Association Annual Congress, June 2017; Madrid, Spain.