First-line treatment with the Bruton’s tyrosine kinase inhibitor zanubrutinib plus the anti-CD20 monoclonal antibody obinutuzumab and the BCL2 inhibitor venetoclax appeared to be safe and active in previously untreated patients with TP53-mutated mantle cell lymphoma, based on the results of the multicenter phase II BOVen trial published by Kumar et al in the journal Blood.
“TP53-mutant mantle cell lymphoma is associated with poor survival outcomes with standard chemoimmunotherapy,” the investigators commented. “The 2-year progression-free survival of 72% compares favorably with previously reported outcomes with chemoimmunotherapy.”
Study Details
Initially, a total of 25 patients received zanubrutinib (160 mg twice daily) and obinutuzumab (1,000 mg on days 1, 8, and 15 of cycle 1 and on day 1 of cycles 2 and 8). Venetoclax was added after two cycles, with weekly dose ramp-up to 400 mg daily. After 24 cycles, treatment was discontinued in the patients who were in complete remission with immunosequencing assay–determined undetectable measurable residual disease (MRD). The primary efficacy endpoint was met if at least 11 patients were progression-free at 2 years.
Key Findings
The best overall response rate was 96% (n = 24 of 25), and the complete response rate was 88% (n = 22 of 25). The rates of undetectable MRD at sensitivity thresholds of 10-5 and 10-6 were 95% (n = 18 of 19) and 84% (n = 16 of 19), respectively, at cycle 13. With a median follow-up of 28.2 months, the 2-year progression-free survival rate was 72%, the disease-specific survival rate was 91%, and the overall survival rate was 76%. The most common side effects were generally low grade and included diarrhea (64%), neutropenia (32%), and infusion-related reactions (24%).
“[The combination of zanubrutinib, obinutuzumab, and venetoclax] was well tolerated and met its primary efficacy endpoint in TP53-mutant mantle cell lymphoma,” the investigators concluded. “These data support its use and ongoing evaluation.”
Disclosure: For full disclosures of the study authors, visit ashpublications.org.
