Establishing non-inferiority of rituximab plus lenalidomide in the treatment of advanced previously untreated follicular lymphoma

Vollständiger Abstract

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Abstract Background and purpose The current standard of care for first-line treatment for people with advanced (stage 3 or 4) follicular lymphoma (FL) is chemotherapy plus rituximab. Rituximab plus lenalidomide is an oral treatment which has been shown to be an effective alternative treatment. In order to support a license extension application for lenalidomide in this indication, NHS England considered the re-analysis of the RELEVANCE trial to determine whether the treatments can be shown to be statistically and clinically non-inferior, before its dismemberment in 2025. Materials and methods A Bayesian non-inferiority analysis compared rituximab plus lenalidomide with rituximab plus chemotherapy in patients with untreated FL. The primary outcome was overall response rate (ORR). Comparisons to pre-specified non-inferiority margins (− 7% and − 12%) were performed using the intention-to-treat, investigator-assessed population from the RELEVANCE trial. Normal likelihoods were specified using published estimates of the natural history response rate and treatment effect, with default non-informative (flat) priors, and posterior probabilities of exceeding each non-inferiority margin estimated. Results The posterior probability that rituximab plus lenalidomide was inferior to the pre-specified non-inferiority margins was extremely low post-induction (< 0.01% for − 7% margin and − 12% margin); and at 120 weeks (0.003% for − 7% margin and < 0.01% for − 12% margin). Conclusion The findings are consistent with non-inferiority of rituximab plus lenalidomide compared to rituximab plus chemotherapy for patients with untreated FL when using ORR as the outcome.