RELEVANCE phase III 10‑year results: R2 vs immunochemotherapy in previously untreated advanced FL

Results from the preplanned 10-year final analysis of the multinational, randomized, open-label, phase III RELEVANCE trial (NCT01476787; NCT01650701), evaluating rituximab + lenalidomide (R2; n = 513) vs rituximab-based immunochemotherapy (R-Chemo; n = 517) in adults with previously untreated Grade 1–3a follicular lymphoma (FL), were published in Blood by Gower et al. Primary endpoints included complete response confirmed/unconfirmed (CR/CRu) rate at 120 weeks and progression-free survival (PFS) by independent review committee (IRC); this long-term analysis allowed for mature assessment of PFS.

Key data: At a median follow-up of 118.2 months, median PFS was comparable between groups at 110.6 months (95% confidence interval [CI], 84.4–not reached [NR]) with R2 and 102.8 months (95% CI, 82.8–NR) with R-Chemo (p = 0.80); estimated PFS rates were 46.4% and 46.6%, respectively. Median overall survival (OS) and time-to-next lymphoma treatment (TTNLT) were NR in either group; estimated 10-year OS rates were 82.4% vs 81.1% and estimated 10-year TTNLT rates were 62.2% vs 66.3% for R2 vs R-Chemo. No new safety findings emerged; 1.5% of patients experienced a Grade 5 treatment-emergent adverse event (TEAE). The cumulative incidence of second primary malignancies (SPMs) was 2.11 cases per 100 patient-years, with comparable rates in both treatment groups.

Key learning: These long-term data continue to support R2 as a chemotherapy-free first-line treatment strategy for previously untreated advanced FL and may provide a useful benchmark for evaluating emerging non-chemotherapy combinations in this setting.