Dr Pearse on the BOVen Trial of BTK Inhibitor Combinations in TP53-Mutant MCL

William B. Pearse, MD, assistant professor, medicine, University of California, San Diego School of Medicine, explains how the ongoing phase 2 BOVen trial (NCT04463025) could shift the current roles of available BTK inhibitors and potentially address unmet needs in TP53-mutant mantle cell lymphoma (MCL).

Addressing unmet needs must be a priority when designing clinical trials that incentivize the referral of patients with MCL, Pearse begins. Since MCL is considered a rarer lymphoma, it can be challenging to accrue specific patient populations for clinical trials, he explains. One significant area of clinical need in this disease is for patients whose tumors express TP53mutations, as they tend to have poorer outcomes with conventional induction therapies, Pearse states. Patients with TP53-mutated MCL often exhibit reduced responses to cytarabine-based induction regimens and experience inferior longitudinal outcomes compared with those who do not harbor this mutation, he adds.

The BOVen trial presents a crucial opportunity to explore how BTK inhibition combined with other targeted agents may serve as a chemotherapy-sparing approaches with meaningful activity, particularly for patients with TP53 mutations, Pearse continues. The trial is assessing the efficacy and safety of zanubrutinib (Brukinsa) in combination with venetoclax (Venclexta) and obinutuzumab (Gazyva) in the frontline setting. It aims to provide valuable insights into potential treatment strategies for this subset of patients, he notes.

Early data presented at the 2023 ASH Annual Meeting have shown that the combination elicited higher response rates and 2-year progression-free survival (PFS) rates vs those historically seen with chemoimmunotherapy in a cohort of 25 patients. The best overall response rate (ORR) was 96%, and this included a complete response rate of 88%. At a median follow-up of 23.3 months, the 2-year PFS rate was 72% and the median PFS was not reached; 11 patients were progression free at 2 years. The regimen was also reported to be generally well tolerated.

Overall, the BOVen trial holds promise in advancing the understanding and management of MCL, especially in addressing the needs of patients with TP53 mutations, Pearse concludes.