Combination of lenalidomide and rituximab overcomes rituximab-resistance in patients with indolent B-cell and mantle cell lymphomas
Mené sur 50 patients atteints d'un lymphome à cellules du manteau ou à cellules B ayant développé une résistance au rituximab, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité de l'ajout de lénalidomide au rituximab pour surmonter la résistance thérapeutique
Purpose: Lenalidomide, an immunomodulatory agent that enhances antibody dependent cell mediated cytotoxicity, has the potential to synergize with rituximab, an anti-CD20 monoclonal antibody. We hypothesized that the addition of lenalidomide to rituximab would improve clinical outcomes in patients with B-cell lymphomas who were previously rituximab resistant, defined as no response to or progression of lymphoma within 6 months of rituximab-based therapy. Experimental Design: We conducted a single center, phase II trial in patients with indolent B-cell or mantle cell lymphomas who were previously rituximab resistant (ClinicalTrials.gov NCT00783367). Patients received lenalidomide 10mg daily for 8 weeks, and then received four weekly doses of rituximab 375 mg/M2; lenalidomide continued during and after rituximab. Response to therapy was assessed after 8 weeks of lenalidomide and 12 weeks after first dose of rituximab. The primary endpoint was overall response rate (ORR) after lenalidomide and rituximab. Results: Fifty patients were enrolled and 43 patients completed both response assessments. ORR after 8 weeks of lenalidomide was 30.2%; 12 weeks after the addition of rituximab to lenalidomide, ORR increased to 62.8% (N=43). For all patients (N=50), median progression-free survival (PFS) is 22.2 months (median follow-up 39.2 months). PFS after lenalidomide-rituximab was significantly longer than the PFS for the antecedent regimen used to define rituximab resistance (22.2 versus 9.13 months, p=0.0004). Conclusions: This trial is the first to show that the combination of lenalidomide and rituximab overcomes prior rituximab-resistance in patients with indolent B-cell and mantle cell lymphomas.