At the 2017 ASH Annual Meeting in Atlanta, GA, Dr. Brian Koffman interviewed Dr. George Follows from the Cambridge University Hospital in the UK regarding clinical data regarding the combination of venetoclax and rituximab.
Venetoclax is a highly selective B-cell lymphocyte 2 (Bcl-2) antagonist approved as a monotherapy in patients who have relapsed/refractory CLL with del17. BcL-2 is a member of a family of proteins that function to regulate apoptosis (cell death). Bcl-2 that is often overexpressed in CLL cells resulting in tumor survival and resistance to traditional chemotherapy. For more information about how Bcl-2 functions in the development and treatment of CLL, please see the interview with Dr. Michael Choi published in 2015. For more information about venetoclax, please read the article written in 2017 by Tom Henry, a CLL patient and pharmacist.
Dr. John F. Seymour from Australia reported at ASH 2017 on a Phase III study in which patients with relapsed or refractory CLL were randomized to receive either venetoclax plus rituximab or bendamustine plus rituximab. Rituximab is a monoclonal antibody against CD20 which is expressed on CLL cells. Treatment with rituximab is associated with CLL cell death. Therefore, by combining venetoclax and rituximab, it is hoped that they will work together to increase CLL cell death.
Take Away Points:
- 389 patients with relapsed or refractory CLL were enrolled in this trial
- The estimated progression-free survival was 84.9% among patient receiving venetoclax and 36.3% among those receiving bendamustine
- Overall survival and response rates were also increased in patients receiving venetoclax compared to bendamustine
- A serious adverse event (grade 3 or 4), neutropenia was associated with the venetoclax combination. Serious febrile neutropenia or infections occurred with the same frequency in both study groups.
Summary
Venetoclax is an antagonist of Bcl-2 and functions to induce CLL cell death. Rituximab also functions to increase CLL cell death. The combination of the two was tested against bendamustine plus rituximab and showing improvements in progression-free survival and overall survival.
The potential advantages of combining venetoclax and rituximab is a potential increase in cell death with less adverse events compared to chemotherapy.
More clinical trials are necessary to further elucidate the effectiveness of venetoclax plus rituximab; however, these results are encouraging.
You can watch my interview with Dr. Follows below or read the transcript here:
Here is the link to the ASH abstract:
Joanne Faysal 4/17/18
