Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy.

The SAKK 35/10 phase-2 trial (NCT01307605), developed by the Swiss Group for Clinical Cancer Research (SAKK) and the Nordic Lymphoma Group (NLG), compared the activity of rituximab versus rituximab plus lenalidomide in untreated follicular lymphoma patients in need of systemic therapy. Patients were randomized to rituximab (375 mg/m2 IV on day 1, weeks 1-4, repeated week 12-15 in responding patients) or to rituximab (same schedule) in combination with lenalidomide (15 mg PO daily for 18 weeks). Primary endpoint was complete response (CR/CRu) rate at 6 months. In total, 77 patients were allocated to rituximab monotherapy and 77 to the combination (47% poor-risk FLIPI in each arm). A significantly higher CR/CRu rate at 6 months was documented in the combination arm by the investigators (36%, 95% CI: 26-48% vs. 25%, 95% CI: 16-36%) and confirmed by an independent response review of only CT scans (61%, 95% CI: 49-72% vs. 36%, 95% CI: 26-48%). After a median follow-up of 4 years, significantly higher 30-month CR/CRu rates, longer progression-free survival (PFS) and time to next treatment (TTNT) were observed for the combination. Overall survival (OS) rates were similar in both arms (≥ 90%). Toxicity grade ≥3 was more common in the combination arm (56% vs. 22% of pts), mainly represented by neutropenia (23% vs. 7%). Addition of lenalidomide to rituximab significantly improved CR/CRu rates, PFS, and TTNT, with higher but expected and manageable toxicity. The excellent OS in both arms suggests that chemotherapy-free strategies should be further explored.