Results From the Full Population of a Phase II Trial of Venetoclax in CLL With 17p Deletion
In an article published in the Journal of Clinical Oncology, Stilgenbauer et al reported findings from the full population of the phase II trial that supported the 2016 approval of venetoclax (Venclexta) in the treatment of previously treated chronic lymphocytic leukemia (CLL) with 17p deletion.
Study Details
Venetoclax approval was based on findings in 107 patients in the international phase II trial, which began enrollment in June 2013. An additional 51 patients (including 5 previously untreated patients) were enrolled in a safety expansion cohort. All patients received venetoclax at 400 mg/d after an initial dose ramp-up. The current report provides an analysis of outcomes in all 158 patients, including minimal residual disease (MRD) assessed by flow cytometry. Data cutoff for the analysis was in April 2017.
Responses
Patients had a median of two prior therapies (range = 0–10), 71% had a TP53 mutation, and 48% had nodes ≥ 5 cm. Median time on venetoclax was 23.1 months (range = 0–44.2 months), and median time on study was 26.6 months (range = 0–44.2 months).
Among all 158 patients, objective response was observed in 122 (77%), with complete remission/complete remission with incomplete marrow recovery in 32 patients (20%). Median duration of response was 33.2 months. Progression-free survival at 24 months was 54%.
Among 16 patients who had received prior kinase inhibitor treatment, response was observed in 10 (63%), median duration of response was not reached, and 24-month progression-free survival was 50%. On intent-to-treat analysis, 48 patients (30%) had MRD below the cutoff of 10-4 CLL cells in blood; MRD below cutoff was observed in 48% (48 of 101) patients evaluated for MRD.
Adverse Events
The most common adverse events of any grade were neutropenia (42%), diarrhea (39%), nausea (37%), anemia (25%), fatigue (23%), and thrombocytopenia (20%). Grade 3 or 4 adverse events occurred in 75% of patients, with the most common being neutropenia (40%), thrombocytopenia (15%), and anemia (15%). Serious adverse events occurred in 58%, with the most common being pneumonia (10%), autoimmune hemolytic anemia (5%), and pyrexia (5%).
The investigators concluded, “Venetoclax achieves durable responses and was well tolerated in patients with [17p deletion] CLL. A high rate of blood MRD < 10-4 was achieved in this high-risk population.”
The study was funded by AbbVie and Genentech.
Stephan Stilgenbauer, MD, of the Department of Internal Medicine III, Ulm University, is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
