Assessing Zanubrutinib, Obinutuzumab, Venetoclax for Previously Untreated CLL

Pharmacy Times interviewed Jacob D. Soumerai, MD, assistant professor, medicine at Harvard Medical School and a clinical investigator in lymphoma, medicine at Massachusetts General Hospital, on his recent presentation at the American Society of Hematology Annual Meeting and Exposition 2021 on minimum residual disease (MRD)-driven time limited therapy with zanubrutinib, obinutuzumab, and venetoclax (BOVen) in previously untreated chronic lymphocytic leukemia (CLL).

Jacob D. Soumerai: The BOVen triplet combination is comprised of 3 highly active agents zanubrutinib, obinutuzumab, and venetoclax. We know that venetoclax and obinutuzumab (VO) administered over 1 year is a standard option for patients with newly diagnosed CLL and achieves durable undetectable MRD remissions.

Zanubrutinib is a second generation Bruton's tyrosine kinase (BTK) inhibitor, which has 100% BTK occupancy on lymph nodes, minimal inhibition of BTK—this is important because this can interfere with CD20 antibody activity—and a favorable safety profile based on randomized trials, notably with less atrial fibrillation.

We hypothesized here that zanubrutinib added to VO would achieve frequent durable undetectable MRD responses, and that this may have the potential to improve outcomes for patients.

But something very unique about this study is that we are responding to the knowledge that there's a lot of heterogeneity in CLL—some patients may relapse early and may require additional agents or treatment duration, while others may maintain durable remissions with less therapy. There's really a critical need for clinically validated predictive markers to personalize therapy and to identify high-risk patients potentially for further research into mechanisms of resistance. So here we explored the MRD as a biomarker for directing treatment duration in the BOVen clinical trial.