Zanubrutinib in Combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) for Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL): Interim Results from a Phase 1b Clinical Trial

Introduction. Although most patients (pts) with DLBCL are cured with R-CHOP, ~40% develop refractory or relapsed disease. Several studies have shown a potential therapeutic role for BTK inhibitors in DLBCL. In the phase 3 PHOENIX trial of pts with DLBCL, the addition of ibrutinib to R-CHOP failed to improve overall outcomes. However, in pts <60 years, ibrutinib plus R-CHOP improved the progression-free (PFS) and overall (OS) survivals. The age-based difference in outcomes with ibrutinib plus R-CHOP may be due to greater toxicity and reduced R-CHOP dose intensity with this combination in older pts. We hypothesized that zanubrutinib, a 2 nd-generation BTK inhibitor with greater selectivity for BTK and improved safety compared with ibrutinib, could be safely combined with R-CHOP and improve outcomes.