Phase 3 SELENE Study: Ibrutinib Plus BR/R-CHOP in Previously Treated Patients with Follicular or Marginal Zone Lymphoma.

The phase 3 SELENE study evaluated ibrutinib + chemoimmunotherapy (CIT; bendamustine and rituximab [BR] or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]) in 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 six cycles of BR/R-CHOP. Primary endpoint 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] [95% CI], 0.806 [0.626-1.037]; P = .0922). Median overall survival was not reached in either arm (HR [95% CI], 0.980 [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 to placebo + CIT. The safety profile was consistent with known profiles of ibrutinib and CIT. This trial was registered at www.clinicaltrials.gov as # NCT01974440.