By Richard Furman, M.D. Patients with CLL who relapse after or become refractory to treatments like ibrutinib or idelalisib have poor outcomes. Venetoclax (also known as ABT-199) is an oral inhibitor of the BCL-2 (B-cell lymphoma 2) protein. The BCL-2 protein plays a critical role in preventing cells from undergoing apoptosis (cell death), in healthy cells and in CLL cells. In a recent study presented at the 2016 annual ASH meeting, we evaluated the effectiveness of venetoclax in treating people who relapsed after or were refractory to ibrutinib or idelalisib.
During this phase 2 trial 64 people with CLL were divided into two arms. The first arm consisted of those who were relapsed or refractory to ibrutinib, while the second arm included those who were relapsed or refractory to idelalisib. 43 patients were enrolled in the first arm and were on ibrutinib for a median of 17 months, receiving venetoclax for a median of 13 months, while 21 patients in the second arm were on idelalisib for a median of 8 months and received venetoclax for a median of 9 months. Thirty-nine patients in the ibrutinib arm and 21 patients in idelalisib arm completed the full course of treatment. The objective response rate as determined by investigators was 69% (27/39) for people who were ibrutinib resistant, and 57% (12/21) for the idelalisib resistant. At the time of analysis no median progression free survival or overall survival has been reached. Overall the progression free survival was 72% and overall survival was 90% for all participants.
The results from this trial demonstrate that venetoclax has displayed robust activity and is tolerable for people whose CLL has progressed after treatment with ibrutinib and idelalisib. Although there have been few complete responses, patients will continue to be monitored to chart any further improvements. Additional follow up will be required to assess how long lasting venetoclax responses will be.
New Developments in Lymphoma 