Assessing Primary Endpoint Trial Results for BOVen Therapy in Previously Untreated CLL
Jacob D. Soumerai, MD, of Harvard Medical School and Massachusetts General Hospital, addresses the primary endpoint in the trial assessing zanubrutinib, obinutuzumab, and venetoclax in previously untreated chronic lymphocytic leukemia.
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 primary point was undetectable minimum residual disease [MRD] at a threshold of 10 to the -4, or 1 CLL cell per 10,000 leukocytes, and the peripheral blood and bone marrow they had to achieve uncheckable MRD in both. We used a flow cytometry assay because at the time this was the only clinically validated assay in CLL when the study was initiated.
The primary endpoint of the trial was met 89%, or 33 of 37 patients, attained undetectable MRD at 10 to the -4 in both the peripheral blood and the bone marrow, all of whom met pre-specified undetectable MRD criteria treatment discontinuation criteria and stopped therapy after a meeting of 10 months of treatment, and this includes 2 cycles of zanubrutinib and obinutuzumab before venetoclax is initiated.
With the median follow-up of 25 months and importantly a median post-treatment surveillance follow-up of 15.8 months, 94% of patients, or 31 of 33 patients, who had achieved undetectable MRD and stopped therapy in an undetectable MRD remission remained in ongoing undetectable MRD remission at 10 to the -4 threshold.
One patient with recurrent detectable MRD, which developed 1 year after completing therapy, went on to receive venetoclax and zanubrutinib again, and re-treatment was associated with undetectable MRD remission in the peripheral blood for a second time.