John C. Byrd, MD
An interim analysis of a phase II trial reported by Jones et al in The Lancet Oncology indicates that venetoclax (Venclexta) produces a response in a high proportion of patients with chronic lymphocytic leukemia (CLL) progressing on or after ibrutinib (Imbruvica) treatment. John C. Byrd, MD, of The Ohio State University Comprehensive Cancer Center, Columbus, is the corresponding author of The Lancet Oncology article.
The study included 127 patients with relapsed or refractory CLL from 15 U.S. sites. The current analysis included 91 patients who had received ibrutinib treatment as their last prior therapy with a B-cell receptor inhibitor. Treatment consisted of oral venetoclax starting at 20 mg/d, with stepwise ramp-up over 5 weeks to 400 mg/d. The study is ongoing.
At the time of analysis, median follow-up was 14 months. An objective response was observed in 59 patients (65%), including a complete response or complete response with incomplete bone marrow recovery in 8 patients (9%). Stable disease was observed in 24% of patients. Median duration of response was not reached. Median progression-free survival was 24.7 months, with a 12-month rate of 80%. Median overall survival was not reached, with a 12-month rate of 91%.
The most common grade 3 or 4 adverse events were neutropenia (51%), thrombocytopenia (29%), anemia (29%), decreased white blood cell count (19%), and decreased lymphocyte count (15%). Serious adverse events occurred in 50%, and treatment was discontinued due to adverse events in 7%. No treatment-related deaths were observed.
The investigators concluded: “The results of this interim analysis show that venetoclax has durable clinical activity and favourable tolerability in patients with relapsed or refractory [CLL] whose disease progressed during or after discontinuation of ibrutinib therapy. The durability of response to venetoclax will be assessed in the final analysis in 2019.” ■