Bayesian reanalysis supports rituximab–lenalidomide non-inferiority in follicular lymphoma

A Bayesian reanalysis of the RELEVANCE trial found strong statistical evidence that rituximab plus lenalidomide was not inferior to rituximab plus chemotherapy by the trial’s prespecified margins when overall response rate was used as the primary outcome. The analysis focused on patients with previously untreated follicular lymphoma and was conducted to assess whether the oral regimen could support a licence extension application for lenalidomide in first-line treatment. The article, published in BMC Cancer on 29 August 2026, reports that the posterior probabilities of falling below either margin were extremely low after induction and remained very low at 120 weeks.

First-line treatment for advanced follicular lymphoma, defined as stage 3 or 4 disease, has conventionally involved chemotherapy together with rituximab. Rituximab plus lenalidomide is an oral treatment that has previously been shown to be an effective alternative. The new work did not constitute a newly randomized trial: it was a reanalysis of data from the RELEVANCE trial, using the intention-to-treat population assessed by investigators. This distinction matters because the objective was to determine whether the two approaches could be shown to be statistically and clinically non-inferior under a specified statistical framework, rather than to initiate a new prospective comparison.

For its primary endpoint, the investigators examined overall response rate, the proportion of patients whose disease responded to treatment. They compared rituximab plus lenalidomide with rituximab plus chemotherapy against two prespecified non-inferiority margins of −7% and −12%. The Bayesian model specified normal likelihoods using published estimates of the natural-history response rate and the treatment effect, together with default flat, or non-informative, prior distributions. Posterior probabilities were then estimated for each margin, allowing the data to be expressed as the probability that the difference between treatments was sufficiently small for non-inferiority to be supported.

The results showed a posterior probability of less than 0.01% for being inferior at either the −7% or −12% margin after induction. At 120 weeks, the corresponding probability remained exceptionally low, at 0.003% for the −7% margin and less than 0.01% for the −12% margin. The investigators therefore concluded that the findings were consistent with non-inferiority of rituximab plus lenalidomide relative to rituximab plus chemotherapy on the basis of overall response rate. The analysis addresses whether the treatments met a prespecified threshold for an acceptable difference, not whether one regimen produced a superior average response.

The findings provide formal support for rituximab plus lenalidomide as a potential alternative in previously untreated follicular lymphoma, but the scope of the reported analysis should be considered. The supplied study report centers on overall response rate and gives no corresponding results here for progression-free survival, overall survival, adverse events, quality of life or the number of patients in each group. Its conclusion is also tied to the chosen likelihood model, prior distributions and non-inferiority margins. Accordingly, the result supports consistency with non-inferiority for the evaluated response outcome and population rather than establishing universal clinical equivalence across all outcomes. The analysis was undertaken before the RELEVANCE trial was dismantled in 2025, and the article is an early open-access version of peer-reviewed research that remains subject to further editorial changes.

Subject of Research: Bayesian non-inferiority analysis of rituximab plus lenalidomide versus rituximab plus chemotherapy in previously untreated follicular lymphoma

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

Article References: Perks, J., Allen, A., Farmer, C., Robinson, S., & Melendez-Torres, G. J. (2026). Establishing non-inferiority of rituximab plus lenalidomide in the treatment of advanced previously untreated follicular lymphoma. BMC Cancer. https://doi.org/10.1186/s12885-026-16836-z

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16836-z

Keywords: follicular lymphoma, rituximab, lenalidomide, non-inferiority, Bayesian analysis, RELEVANCE trial, overall response rate, chemotherapy, Establishing, plus, treatment, advanced