CHESS phase II: Zanubrutinib + rituximab followed by shortened chemoimmunotherapy in 1L MCL

Results from the phase II, investigator-initiated, open-label, single-arm, multicenter CHESS trial (NCT04624958), evaluating zanubrutinib + rituximab for 12 cycles (Part A) followed by shortened chemoimmunotherapy (4 cycles of rituximab + dexamethasone + cytarabine + oxaliplatin [R-DHAOx]) (Part B) as first-line (1L) treatment in adults aged 18–75 years with previously untreated Stage II–IV mantle cell lymphoma (MCL; N = 42), were published in Nature Communications by Zhang et al. The primary endpoint was complete response (CR) rate at Part A completion.

Key data: The CR rate at Part A completion was 88% (95% confidence interval [CI], 74–96); the remaining 12% had progressive disease (PD). The median time to CR was 4 months, while the measurable residual disease (MRD)-negative CR rate was 74% (95% CI, 58–86). Among the 39 patients who completed Part B, the CR rate was 92% (95% CI, 79–98); the remaining 8% had PD. At a median follow-up of 23 months, median progression-free survival (PFS) and overall survival (OS) were not reached; 2‑year PFS and OS rates were 85% (95% CI, 75–97) and 90% (95% CI, 75–100), respectively. Grade 3–4 treatment-related adverse events (TRAEs) were mainly hematologic, including neutropenia (7%) and lymphocytopenia (7%) in Part A and thrombocytopenia (77%), leukocytopenia (59%), and neutropenia (49%) in Part B.

Key learning: Zanubrutinib + rituximab induction followed by shortened chemoimmunotherapy demonstrated encouraging efficacy and a manageable safety profile as a 1L treatment strategy in previously untreated MCL, with the potential to reduce chemotherapy exposure while maintaining deep remissions.