Phase 2 trial of frontline zanubrutinib-rituximab followed by shortened chemoimmunotherapy for mantle cell lymphoma

A combination of the BTK inhibitor ibrutinib with rituximab has shown promising efficacy in mantle cell lymphoma (MCL). The phase 2 CHESS trial at Sun Yat-sen University Cancer Center (Guangzhou, China) evaluated the second-generation BTK inhibitor zanubrutinib plus rituximab as induction, followed by shortened immunochemotherapy as frontline treatment for stage II-IV MCL requiring immediate therapy. 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 af part A completion. Forty-two patients were enrolled. The CR rate was 88% (95% CI 74-96) at part A completion and 86% (72-95) at part B completion. The most common grade 3-4 adverse events were neutropenia (7%) in part A and thrombocytopenia (77%) and neutropenia (49%) in part B. The authors conclude that zanubrutinib-rituximab followed by shortened R-DHAOx is effacious with manageable safety as frontline therapy for MCL.