A phase 1/1b study of combined rituximab, bendamustine, and ibrutinib in patients with previously untreated and relapsed/refractory non-Hodgkin's lymphoma
Mené sur 48 patients atteints d'un lymphome non hodgkinien récidivant, cet essai de phase 1/1b évalue la toxicité et l'efficacité d'un traitement combinant ibrutinib, rituximab et bendamustine
Ibrutinib has single agent activity of 22-68% in relapsed B-cell non-Hodgkin's lymphoma (NHL). This study evaluated the safety and efficacy of ibrutinib combined with rituximab (R) and bendamustine. Patients received R 375 mg/m2 day 1, bendamustine 90 mg/m2 days 1 and 2, and ibrutinib (280 or 560 mg) days 1-28 every 28 days for 6 cycles followed by ibrutinib alone until progression. Forty-eight patients enrolled, including 12 patients with follicular lymphoma (FL), 16 with diffuse large cell lymphoma (DLCL), and 17 with mantle cell lymphoma (MCL). No dose limiting toxicities were observed. Patients received a median of 8 cycles, with 26 completing 6 cycles and continuing ibrutinib alone in cycles 7-34. The overall response rate (ORR) was 72%, with 52% complete responses (CR). By histology, the ORR was 94% (76% CR) in MCL, 37% (31% CR) in DLCL, and 90% (50% CR) in FL. Grade 3-4 toxicities included lymphopenia (77%), neutropenia (33%), thrombocytopenia (19%), and rash (25%). Median progression-free survival has not been reached (95% CI, 8.7 months - not reached). The recommended phase 2 dose of ibrutinib in combination with R-bendamustine in patients with NHL is 560 mg. The combination has promising efficacy, particularly in MCL and FL.