Ibrutinib plus lenalidomide and rituximab has promising activity in relapsed/refractory non-germinal center B-cell DLBCL

The outcome of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is poor, particularly in patients ineligible for stem cell transplantation or who fail induction therapy or salvage therapy. The phase 1b portion of this open-label, dose-escalation (3+3+3 design) study examined the maximum tolerated dose (MTD) and preliminary safety and activity of the regimen in transplant-ineligible adults with histologically confirmed relapsed/refractory DLBCL after {greater than or equal to}1 prior therapy. Patients received once-daily 560 mg ibrutinib, 375 mg/m2 IV rituximab Day 1 of Cycles 1-6, and 10, 15, 20, or 25 mg lenalidomide Days 1-21 of each 28-day cycle; 45 patients were treated; median time since diagnosis was 14.1 months; 51% had non-germinal center B-cell (non-GCB) DLBCL; 33% had transformed DLBCL; 60% were refractory and 27% were primary refractory. Due to dose-limiting toxicities, a de-escalation cohort (10 mg lenalidomide) was initiated and, with subsequent re-escalation up to 25 mg lenalidomide, the MTD was not reached. In response-evaluable patients, the overall response rate (ORR) was 44% (complete response [CR], 28%); among them, the ORR was 65% (CR, 41%) in non-GCB and 69% and 56% in relapsed (n = 16) and secondary refractory (n = 27) disease, respectively. Overall and for non-GCB, median response duration was 15.9 months, with 2 patients on therapy beyond 3 years. Phase 2 was initiated with 20 mg lenalidomide in relapsed/refractory non-GCB, while the phase 1b 25-mg lenalidomide cohort was being completed; an additional 25-mg cohort in phase 2 is currently ongoing. This study was registered at www.clinicaltrials.gov as #NCT02077166.