New Treatment Potential for TP53-Mutated MCL


Anita Kumar, MD, discusses findings from the phase 2 study of zanubrutinib, obinutuzumab, and venetoclax in TP53-mutant mantle cell lymphoma presented at ASH 2023.

The targeted therapy combination of obinutuzumab (Gazvya), zanubrutinib (Brukinsa), and venetoclax (Venclexta; BOVen) showed promising results in treating P53-mutant mantle cell lymphoma (MCL), a difficult-to-cure form of cancer. Patients receiving BOVen achieved high rates of survival and disease-free status after 2 years, exceeding expectations for this aggressive subtype. Moreover, those who completed therapy demonstrated near-complete remission, with over 80% achieving undetectable levels of cancer cells. These findings suggest that BOVen could be a game-changer for patients with P53-mutant MCL, offering significantly improved outcomes compared to standard treatments. Further investigation is needed, but this study provides strong evidence for the potential of BOVen as a powerful new treatment option.

At the American Society of Hematology 2023 Annual Meeting, Anita Kumar, MD, associate attending physician and lymphoma specialist at Memorial Sloan Kettering Cancer Center, discusses findings from the phase 2 trial (NCT03824483) evaluating BOVen in P53-mutant MCL.


0:09 | P53-mutant mantle cell lymphoma is a high-risk entity. Unfortunately, patients with this subtype of mantle cell lymphoma have poor outcomes with standard chemo-immunotherapy. The idea for this study was to develop a combination of biologically targeted therapies. The obinutuzumab, zanubrutinib, and venetoclax [BOVen] combination was used to treat this high-risk subgroup of patients. And we hypothesized that this combination would be more efficacious than standard chemo-immunotherapy.

0:42 | Two-year progression-free survival associated with the BOVen treatment regimen for P53-mutant mantle cell lymphoma was 72%. And the 2-year overall survival was 75%. The disease-free survival at 2 years was 88%. The disease-free survival is superior to the progression-free survival because we did observe some deaths that were not related to disease, reflected some excess deaths related to COVID-19 because this study took place during the context of the COVID-19 pandemic. We found that at 2 years, there were 11 patients who were progression-free and so therefore, the primary endpoint of the study was met.

1:24 | We look at the patients who completed 24 cycles of therapy, the 11 patients, all of these patients achieved a complete remission. Of the 11 patients, 1 we could not assess the minimal residual disease [MRD] status because they didn't have a baseline tumor specimen available for analysis. But in the remaining 10 patients, 80% or 8 patients achieved an undetectable MRD status and stopped therapy and then 2 of the patients were a CR but had detectable minimal residual disease. And those patients continued on the oral drugs of the zanubrutinib and obinutuzumab.

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