SAKK 35/14 randomized trial of rituximab with or without ibrutinib for patients with untreated follicular lymphoma.

The randomized phase II SAKK 35/14 trial, conducted by the Swiss Group for Clinical Cancer Research (SAKK) and the Nordic Lymphoma Group (NLG), compared efficacy and safety of rituximab (375 mg/m2 intravenously for 4 weeks followed by maintenance every 2 months for 24 months) plus placebo (arm A) versus the same schedule of rituximab plus ibrutinib (560 mg daily for 24 months, arm B) in patients with advanced follicular lymphoma in need of systemic therapy. The primary end-point, complete remission (CR) rate at 24 months, was 36% in arm A and 40% in arm B, with no statistically significant difference. Three-year progression-free survival (PFS) was 36% in arm A and 45% in arm B, with a hazard ratio of 0.64 (p = 0.057). Three-year overall survival was about 96% in both arms. A higher percentage of patients in arm B experienced grade ≥3 adverse events, but they were manageable. No toxic deaths were observed. Although the primary end-point (CR rate at 24 months) was not met, a trend towards improved PFS with ibrutinib plus rituximab observed at the prespecified significance level of 0.1 may indicate a potential clinical benefit.