Multicenter phase 2 trial of zabrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with TP53 mutation

TP53-mutant mantle cell lymphoma (MCL) is associated with poor survival outcomes with standard chemoimmunotherapy. Dual BTK and BCL2-inhibition with or without anti-CD20 monoclonale antibody therapy has shown promising activity in TP53-mutant MCL. A multicenter phase 2 trial in the USA evaluated zanubrutinib, obinutuzumab, and venetoclax (BOVen) in 25 untreated MCL patients with TP53 mutation. The best overall response rate was 96% 924/25) en the complete response rate was 88% (22/25). Frequency of uMRD5 and uMRD6 at cycle 13 was 95% (18/19) and 84% (16/19). With median follow-up of 28.2 months, the primary endpoint was met with a 2-year progression-free survival rate of 72%, and the 2-year disease-specific and overall survival rates were 91% and 76%, respectively. Common side effects were generally low grade. The authors conclude that BOVen was well tolerated and met its primary efficacy endpoint in previously untreated TP53-mutant MCL.