Six-month Rituximab-Lenalidomide regimen in advanced untreated Follicular Lymphoma: SAKK 35/10 Trial 10-year Update.

The Swiss Group for Clinical Cancer Research (SAKK) and the Nordic Lymphoma Group (NLG) conducted the SAKK 35/10 randomized phase-2 trial (NCT0137605) to compare rituximab (R) alone versus R plus lenalidomide (L) as initial treatment for follicular lymphoma (FL). Patients with grade 1-3a FL, requiring systemic therapy, were randomized to either R (n=77; 375 mg/m2 IV x 1, weeks 1-4) or RL (n=77; R on the same schedule and L at 15 mg daily continuously). Responders (evaluated at 10 weeks) repeated R during weeks 12-15 with or without L (for a total of 18 weeks). Both arms had 47% of patients with a poor risk score on the FL International Prognostic Index (FLIPI). The primary endpoint, complete response (CR)/CR unconfirmed (CRu) rates at 6 months were superior with the combination, and now after a median follow-up of 9.5 years, have translated into a longer duration of response (DoR, median not reached vs 3.2 years; hazard ratio (HR)=0.42, 95% confidence interval (95%CI): 0.21-0.86; p=0.014), progression-free survival (PFS, 9.3 vs 2.3 years HR=0.57, 95% CI: 0.37-0.89; p=0.0128), and time-to-next treatment (TTNT, median not reached vs 2.1 years; HR=0.43, 95% CI: 0.27-0.67; p<0.001). Over 60% of RL responders remained in first CR at 10 years. OS was similar in both arms (77% vs 78% at 10 years, p=0.881). Toxicity was more common with RL but manageable. The SAKK 35/10 trial's long-term results confirmed a durable benefit of a short-term chemotherapy-free first-line RL regimen in symptomatic FL.