Phase 3 SELENE study: ibrutinib plus BR/R-CHOP in previously treated patients with follicular or marginal zone lymphoma
Loretta J. Nastoupil, Georg Heß, Miguel Arturo Pavlovsky, Iwona Danielewicz, Jane A. Freeman, Alejandro Martı́n, Valeria A. Glazunova, Andrew Grigg, Jing‐Zhou Hou, Ann Janssens, Seok Jin Kim, Zvenyslava Masliak, Pam McKay, Francesco Merli, Wataru Munakata, Hirokazu Nagai, Muhıt Özcan, Meir Preis, Tingyu Wang, Melissa Rowe, Monelle Tamegnon, Rui Qin, Todd Henninger, Madeliene Curtis, Donne Bennett Caces, Catherine Thiéblemont, Gilles Salles
Abstract
The phase 3 SELENE study evaluated ibrutinib + chemoimmunotherapy (CIT; bendamustine and rituximab [BR]; or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]) for patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL). Adult patients who had received ≥1 prior line of CIT were randomized 1:1 to oral ibrutinib (560 mg) or placebo daily, plus 6 cycles of BR/R-CHOP. The primary end point was investigator-assessed progression-free survival (PFS). Overall, 403 patients were randomized to ibrutinib + CIT (n = 202) or placebo + CIT (n = 201). Most patients received BR (90.3%) and had FL (86.1%). With a median follow-up of 84 months, median PFS was 40.5 months in the ibrutinib + CIT arm and 23.8 months in the placebo + CIT arm (hazard ratio [HR], 0.806; 95% confidence interval [CI], 0.626-1.037; P = .0922). Median overall survival was not reached in either arm (HR, 0.980; 95% CI, 0.686-1.400). Grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 85.6% and 75.4% of patients in the ibrutinib + CIT and placebo + CIT arms, respectively. In each arm, 13 patients had TEAEs leading to death. The addition of ibrutinib to CIT did not significantly improve PFS compared with placebo + CIT. The safety profile was consistent with known profiles of ibrutinib and CIT. This trial was registered at www.clinicaltrials.gov as #NCT01974440.