Assessing Primary Endpoint Trial Results for BOVen Therapy in 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 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.