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Introduction: Rituximab (R) and lenalidomide (R2) is a highly effective therapy for frontline and relapsed/refractory (R/R) follicular lymphoma (FL) (Fowler 2018, Leonard 2019) and is the standard comparator and backbone therapy in ongoing randomized trials for relapsed FL. The efficacy of R2 in relapsed FL was largely defined by AUGMENT (Leonard 2019) which excluded R refractory patients, in contrast to the current phase 3 studies. Because of limited randomized data on the efficacy of R2 in R-refractory FL (Andorsky 2019) we performed a meta-analysis of FL-specific data to assess the progression free survival (PFS) and response rates of len+anti-CD20 based regimens. We also estimated the OR, CR and PFS rates for R2+X (X = systemic agent). Methods: We searched MEDLINE, EMBASE and ClinicalTrials.gov using keywords “lymphoma” and “lenalidomide” from database inception to Dec. 12, 2025. Clinical trials and observational studies evaluating len with an anti-CD20 mAb (with or without another agent) were potentially eligible, including abstracts. Primary endpoints were overall (OR) and complete response (CR) rates by end of induction, and progression free survival (PFS). A mixed-effects model was used to calculate pooled OR and CR, 1-year PFS estimates and 95% confidence intervals. Study heterogeneity was assessed with the I2 statistic. Patients were pooled according to treatment setting (frontline vs. R/R) and therapy (R2 vs. “R2+X”); a separate analysis of studies that included R-refractory patients was also done. Results: Our search yielded 6627 unique abstracts; 36 met inclusion criteria and were included in the final analysis (15 abstracts, 21 manuscripts). In the pooled analysis of frontline studies, the OR rate for R2 was 85.0% (76.2–95.0, n = 814) compared to 96.1% (93.2–99.1, n = 203) for R2+X, and CR rates were 64.6% (51.4–81.1, n = 1076) and 81.6% (74.3–89.6, n = 211). In the R/R setting, OR rate was 79.9% (74.1–86.1, n = 1090) with R2 and 84% (77.2–91.3, n = 632) with R2 +X, and CR rates were 40.2% (33.1–49.0, n = 1159) and 52% (40.2–67.7, n = 632). Analysis of studies including R-refractory patients showed OR and CR rates of 79.6% (71.9–88.1, n = 852) and 44.2% (36.2–54, n = 921) for R2, and 83.3% (75.5–92.0) and 60.3% (50.0–72.7) for R2+X (n = 577). Pooled 1-year PFS estimates for frontline therapy were 83.5% (73.74–94.59, n = 309) for R2 and 92.5% (81.31–100.00, n = 90) for R2+X. For R/R patients, corresponding estimates were 59% (47.44–74.18) and 44.5% (28.19–70.37). Inter-study heterogeneity was high (I2 > 60%) in most analyses. Conclusions: Our FL-specific meta-analysis demonstrates that the cumulative OR, CR and PFS for R/R FL patients are lower than observed in AUGMENT. Furthermore, our results support the addition of an agent to R2 to improve efficacy, possibly with the greatest benefit observed in R-refractory patients. High inter-study heterogeneity was observed as expected with varying R2 dosing schedules, R2 combinations, sample sizes and trial design. Research funding declaration: JT: Regeneron, Genentech, AbbVie, Pharmacyclics, Genmab, Pfizer, ADC Therapeutics; LF: Roche, Genentech, Genmab, AbbVie, Innate Pharma, Beigene, AstraZeneca; SA: Novartis Keywords: indolent non-Hodgkin lymphoma Potential sources of conflict of interest: L. Falchi Consultant or advisory role: Roche, Genentech, Genmab, AbbVie, Sanofi, Evolveimmune, AstraZeneca, Merck, ADC therapeutics, Seagen, Ipsen, Johnson & Johnson Honoraria: Roche, Genmab, AbbVie, Kite Educational grants: Genmab, AbbVie, Roche, Kite S. Assouline Consultant or advisory role: Roche, AstraZeneca, Novartis, Gilead, Beigene Honoraria: Roche, AstraZeneca, Norvatis, Gilead, Abbvie, Beigene Other remuneration: Speaker's bureau: Roche, Novartis