BOVen Combination Proves Well-Tolerated, With Promising Efficacy, in TP53-Mutant Mantle Cell Lymphoma

Treatment with a combination of the BTK inhibitor zanubrutinib, the CD20 antibody obinutuzumab, and the BCL2 inhibitor venetoclax (BOVen) was well tolerated and showed promising preliminary efficacy in patients with previously untreated, TP53-mutated mantle cell lymphoma (MCL). Lead author Anita Kumar, MD, from the Department of Medicine at Memorial Sloan Kettering Cancer Center in New York, shared the results from this study at the 2021 ASH Annual Meeting.

“TP53-mutant MCL is associated with poor survival outcomes with chemoimmunotherapy and there is no standard frontline treatment for this high-risk patient population,” Dr. Kumar and authors explained. Given the findings of previous studies showing synergy between BTK and BCL2 inhibitors for MCL, the authors evaluated BOVen in a multicenter, investigator-initiated phase II trial.

All patients had previously untreated MCL with TP53 mutation. BOVen was administered in 28-day cycles of:

  • zanubrutinib 160 mg twice daily starting on day 1 of cycle 1
  • obinutuzumab 1,000 mg on days 1 (or split between days 1 and 2), 8, and 15 of cycle 1, day 1 of cycles 2-8
  • venetoclax ramp-up initiated on day 1 of cycle 3 (target 400 mg)

Therapy was administered for at least 2 years, with a primary endpoint of 2-year progression-free survival (PFS).

As of the date of presentation, 12 patients had been enrolled, with a median age of 67.5 years (range = 29-79).

The grade 3 treatment-related adverse events (AEs) were limited to infusion-related reaction (IRR; 17%; 2 patients), elevation of transaminases (8%; 1 patient), and neutropenia (8%; 1 patient) that resolved with granulocyte colony stimulating factor support. The most common treatment-related AEs were low-grade and included IRR (17%; grade 1-2 in 3 patients), neutropenia (17%; grade 1-2 in 2 patients), thrombocytopenia (25%; grade 1 in 3 patients), nausea (33%; grade 1 in 4 patients), elevation of transaminases (17%; grade 1 in 2 patients), and rash (17%; grade 1 in 2 patients).

One patient experienced a treatment-related serious AE (fever without neutropenia) on day 2 of cycle 3. This patient was discharged after brief hospitalization in stable condition with resolution of fever and negative infectious work-up, the authors noted. Furthermore, no dose reductions or modifications were required, and no patients developed laboratory or clinical tumor lysis syndrome.

During a median follow-up of 4 months (range = 0-11 months), one patient had progressive disease and the remaining 11 patients remained on study in continued response. The investigators added that, of the 10 patients who have undergone disease restaging after cycle 3, eight achieved a PET-CR, which two patients maintained at cycle 7.

While the preliminary efficacy is promising for this high-risk subgroup of MCL patients, the duration of follow-up is relatively short, the authors noted, and the findings need to be confirmed in larger studies.