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

Andre Goy, Radhakrishnan Ramchandren, Nilanjan Ghosh, Javier Munoz, David S. Morgan, Nam H. Dang, Mark Knapp, Maria Delioukina, Edwin Kingsley, Jerry Ping, Darrin M. Beaupre, Jutta K. Neuenburg and Jia Ruan

Key Points

  • The safety profile of ibrutinib, lenalidomide, and rituximab in combination was manageable in patients with relapsed/refractory DLBCL

  • The combination demonstrated promising and durable activity in relapsed/refractory DLBCL, particularly in patients with non-GCB 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 as #NCT02077166.

  • Submitted December 13, 2018.
  • Revision received July 19, 2019.
  • Accepted June 16, 2019.