Zanubrutinib-rituximab followed by shortened chemoimmunotherapy as frontline treatment for mantle cell lymphoma (CHESS): a phase II trial

A combination of Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib and rituximab has shown promising efficacy in mantle cell lymphoma (MCL). This phase II trial evaluated the second-generation BTK inhibitor zanubrutinib plus rituximab as induction, followed by shortened chemoimmunotherapy as frontline treatment for MCL (NCT04624958). Eligible patients had histologically confirmed stage II–IV disease requiring immediate therapy and no prior MCL-related systemic treatment. Patients received zanubrutinib-rituximab for up to 12 cycles (part A); those achieving a complete response (CR) or experiencing disease progression proceeded to four cycles of R-DHAOx (rituximab, dexamethasone, cytarabine, and oxaliplatin) (part B). Patients with CR after part B received zanubrutinib maintenance for one year. The primary endpoint was the CR rate at part A completion. Forty-two patients were enrolled. The CR rate at part A completion was 88% (95% confidence interval CI, 74-96), and 86% (95% CI, 72-95) at part B completion. Hematologic toxicities predominated: the most common grade 3-4 adverse events were neutropenia (7%) in part A, and thrombocytopenia (77%) and neutropenia (49%) in part B. In conclusion, zanubrutinib-rituximab induction followed by shortened R-DHAOx is efficacious with manageable safety as frontline therapy for MCL. This strategy allows for a reduction in chemotherapy cycles and warrants validation in randomized controlled trials. Zanubrutinib is a second-generation BTK inhibitor, reported to have fewer off-target toxicities while maintaining comparable efficacy to previous BTK inhibitors. Here, the authors report the phase II CHESS trial evaluating frontline Zanubrutinib (second-generation BTK inhibitor) plus rituximab (anti-CD20) induction, followed by chemoimmunotherapy in patients with mantle cell lymphoma.