LEGEND: A randomised phase II study comparing lenalidomide plus rituximab, gemcitabine, and methylprednisolone (R-GEM-L) to rituximab, gemcitabine, methylprednisolone, and cisplatin (R-GEM-P) in second-line treatment of diffuse large B-cell lymphoma (DLBCL).

TPS8618 Background: Diffuse Large B-cell lymphoma (DLBCL) exhibits high sensitivity to first-line chemo-immunotherapy, however approximately one-third of patients (pts) will relapse. A number of salvage regimens including R-GEM-P (rituximab, gemcitabine, cisplatin and methylprednisolone), are used in the relapsed/refractory (RR) setting, with overall (OR) and complete (CR) response rates of 50-70% and 20-50% respectively. Pts eligible for post-salvage consolidation with autologous stem cell transplantation (ASCT) have an overall survival (OS) of 40% at 3 years, while ASCT-ineligible pts have a very poor prognosis. More efficacious salvage regimens are urgently needed for this patient group. Lenalidomide has shown activity in RR DLBCL (both as monotherapy and in combination with rituximab), and has been safely combined with gemcitabine in pancreatic cancer. In the LEGEND trial R-GEM-L (rituximab 375mg/m2 D1 and 15, gemcitabine 1000mg/m2 D1, 8 and 15, methylprednisolone 1000mg D1-5 and lenalidomide 25mg od D1-21) and R-GEM-P are compared as second-line regimens in RR DLBCL. Methods: This is a randomised phase II open-label multicenter study. 92 eligible pts with RR DLBCL after 1 previous line of therapy, PS 0-2 and FDG-avid disease will be randomised on a 1:1 basis to 3 cycles of R-GEM-P (Arm A) or R-GEM-L (Arm B), following which pts in CR may undergo ASCT if eligible. Response will be assessed according to the Modified IWG 2007 Revised Response Criteria incorporating PET/CT. Following R-GEM-L (+/-ASCT) pts on Arm B and in CR will receive an additional 12 months of single-agent lenalidomide maintenance (25mg od D1-21 every 28 days). The primary endpoint is CR rate following induction chemotherapy. Secondary endpoints include ORR, event free survival (EFS), OS, rates of successful stem cell harvest and toxicity. Sample size was estimated using an optimal Simon 2-stage design (based on a true response probability of ≥60% and closing either arm if <40%, one-sided α: 0.05, 80% power). A total of 46 patients will be recruited to each arm. Clinical trial information: 2012-002620-32.