RESUMEN
BACKGROUND: Lenalidomide, an immunomodulatory drug with antineoplastic and antiproliferative effects, showed activity in many single-group studies in relapsed or refractory mantle cell lymphoma. The aim of this randomised study was to examine the efficacy and safety of lenalidomide versus best investigator's choice of single-agent therapy in relapsed or refractory mantle cell lymphoma. METHODS: The MCL-002 (SPRINT) study was a randomised, phase 2 study of patients with mantle cell lymphoma aged 18 years or older at 67 clinics and academic centres in 12 countries who relapsed one to three times, had Eastern Cooperative Oncology Group performance status of 0-2, at least one measurable lesion to be eligible, and who were ineligible for intensive chemotherpy or stem-cell transplantation. Using a centralised interactive voice response system, we randomly assigned (2:1) patients in a permuted block size of six to receive lenalidomide (25 mg orally on days 1-21 every 28 days) until progressive disease or intolerability, or single-agent investigator's choice of either rituximab, gemcitabine, fludarabine, chlorambucil, or cytarabine. Randomisation was stratified by time from diagnosis, time from last anti-lymphoma therapy, and previous stem-cell transplantation. Individual treatment assignment between lenalidomide and investigator's choice was open label, but investigators had to register their choice of comparator drug before randomly assigning a patient. Patients who progressed on investigator's choice could cross over to lenalidomide treatment. We present the prespecified primary analysis results in the intention-to-treat population for the primary endpoint of progression-free survival, defined as the time from randomisation to progressive disease or death, whichever occurred first. Patient enrolment is complete, although treatment and collection of additional time-to-event data are ongoing. This study is registered with ClinicalTrials.gov, number NCT00875667. FINDINGS: Between April 30, 2009, and March 7, 2013, we enrolled 254 patients in the intention-to-treat population (170 [67%] were randomly assigned to receive lenalidomide, 84 [33%] to receive investigator's choice monotherapy). Patients had a median age of 68·5 years and received a median of two previous regimens. With a median follow-up of 15·9 months (IQR 7·6-31·7), lenalidomide significantly improved progression-free survival compared with investigator's choice (median 8·7 months [95% CI 5·5-12·1] vs 5·2 months [95% CI 3·7-6·9]) with a hazard ratio of 0·61 (95% CI 0·44-0·84; p=0·004). In the 167 patients in the lenalidomide group and 83 patients in the investigator's choice group who received at least one dose of treatment the most common grade 3-4 adverse events included neutropenia (73 [44%] of 167 vs 28 [34%] of 83) without increased risk of infection, thrombocytopenia (30 [18%] vs 23 [28%]), leucopenia (13 [8%] vs nine [11%]), and anaemia (14 [8%] vs six [7%]). INTERPRETATION: Patients with relapsed or refractory mantle cell lymphoma ineligible for intensive chemotherapy or stem-cell transplantation have longer progression-free survival, with a manageable safety profile when treated with lenalidomide compared with monotherapy investigator's choice options. FUNDING: Celgene Corporation.