ASH 2025: Phase II Trial of Lenalidomide Plus Rituximab (R2) in Previously Untreated Follicular Lymphoma: 15-year Follow-Up Data from MDACC Trial

Several studies have demonstrated the efficacy of lenalidomide plus rituximab, known as R2, in follicular lymphoma (FL). The long-term outcomes of this treatment approach when used in the frontline setting have previously been unknown, but investigators have now been able to analyze data from 15 years of follow-up in the pivotal phase 2 trial. These results were presented by Foundation Lymphoma Scientific Research Mentoring Program (LSRMP) scholar Dai Chihara, MD of MD Anderson Cancer Center.

The original trial included 79 patients with previously untreated FL and a median age of 56 years (range, 29-84 years). About half of participants had high tumor burden and half had low tumor burden. Most participants had low- (45%) or intermediate-risk (41%) disease; 14% had high-risk disease. Participants received a time-limited course (6 or 12 cycles) of lenalidomide and rituximab. In the initial analysis, 99% of participants with available results had a response to treatment, with a best complete response rate of 87%.

Over the course of the study, nearly half of participants (46%) were lost to follow-up (many during the COVID-19 pandemic). Among participants with available outcomes data, 30 experienced disease progression. The 10-year progression-free survival rate was 61%, and the median progression survival was over 16 years. At 30 months, 76% of participants were in a complete response; these people had longer periods of remission than those who did not achieve a complete response at 30 months.

The 10-year overall survival rate was 95%. Over the course of follow-up, 9 participants died; only 1 death was from lymphoma. Overall survival was shorter for people who experienced disease progression within 24 months of treatment, but this difference was not statistically significant.

After nearly 15 years of follow-up, most patients with FL who received frontline R2 remained in remission, demonstrating durable responses even in the absence of maintenance therapy. The investigators noted that these results will serve as an important reference for long-term outcomes in future trials of FL therapies.

This study also included contributions from Foundation SAB member and Chair-elect Christopher Flowers, MD, MS of The University of Texas MD Anderson Cancer Center; and Foundation grantees Paolo Strati, MD of The University of Texas MD Anderson Cancer Center; and Jason Westin, MD of The University of Texas MD Anderson Cancer Center.