Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial

Abstract

Summary Background Standard treatments for indolent non-Hodgkin lymphomas (iNHLs) are frequently toxic, and most patients ultimately relapse. Lenalidomide, an immunomodulatory agent, is effective as monotherapy for relapsed iNHL. The aim of this phase 2 trial (NCT00695786) was to evaluate the efficacy and safety of lenalidomide plus rituximab in untreated, advanced-stage iNHL and determine the combinaton’s effect on the immune system and tumour microenvironment. The primary objective was to determine the number of complete and partial responses. Methods For follicular lymphoma (FL) and marginal zone lymphoma (MZL), lenalidomide was given orally at 20 mg/day on days 1–21 of all 28-day cycles. Dosing for small lymphocytic lymphoma (SLL) began at 10 mg/day to avoid tumour flare. Rituximab was given at 375 mg/m2 body surface area on day 1 of each cycle. Patients responding after 6 cycles could continue therapy for up to 12 cycles. Patients were evaluated for response analysis if they had any post-baseline tumor assessment. Findings The study enrolled 110 patients, and 103 were evaluable for efficacy analysis. All patients were eligible for safety analysis. The most common grade 3 or 4 adverse events were neutropenia (35%), muscle pain (9%), rash (7%), cough/dyspnea (7%), fatigue (5%), thrombosis (5%), and thrombocytopenia (4%). The overall response rate was 90% (93/103) (95% confidence interval [CI] 83–95%). Complete and partial response rates were 63% (95% CI 53–72%) and 27% (95% CI 19–37%), respectively. Eighty-seven percent (95% CI 74–95%) and 11% (95% CI 4–24%) of FL patients achieved complete and partial responses, respectively. Seventy-nine percent of evaluable FL patients remained in remission at 36 months. Interpretation Lenalidomide plus rituximab is well tolerated and highly effective as initial treatment for iNHL. Durable response rates obtained without cytotoxic agents suggest this regimen could replace chemotherapy as the frontline treatment of iNHL. An international phase 3 study (NCT01476787) is ongoing comparing this regimen to chemotherapy in untreated follicular lymphoma. Funding The study was funded by Celgene Corporation and the Richard Spencer Lewis Memorial Foundation.