Goals: Patients (pts) with relapsed iNHL have limited standard treatment options. The immunomodulatory agent lenalidomide shows enhanced activity with rituximab (ie, R2), which recently reported 39.4-mo median PFS in R/R iNHL pts (J Clin Oncol. 2019;37:1188). MAGNIFY is a multicenter, phase IIIb trial in pts with R/R FL gr1-3a, MZL, or MCL (NCT01996865) exploring optimal lenalidomide duration. Materials and methods: Lenalidomide 20 mg/d, d1-21/28 + rituximab 375 mg/m2/wk c1 and then q8wk c3+ (R2) are given for 12c followed by 1:1 randomization in pts with SD, PR, or CR to R2 vs rituximab maintenance for 18 mo. Data presented here focus on induction R2 in efficacy-evaluable FL gr1-3a and MZL pts (FL gr3, tFL, and MCL not included) receiving ≥1 treatment with baseline/post-baseline assessments to analyze the primary end point of ORR by 1999 IWG criteria. Analyses were done in pts refractory to rituximab (R-ref), refractory to both rituximab and alkylating agent (double-ref), and those with relapse or progression ≤2 y of initial diagnosis after 1L systemic treatment (early relapse [ER]). Results: As of June 16, 2019, 393 pts (81% FL gr1-3a; 19% MZL) were enrolled; median follow up 23.7 mo (range, 0.6-57.8) for censored pts (n = 335). Median age was 66 y (range, 35-91), 83% had stage III/IV disease, with a median of 2 prior therapies (95% prior rituximab-containing). ORR was 69% with 40% CR/CRu. Median DOR was 39.0 mo, and median PFS was 40.1 mo. In R-ref (n = 137), double-ref (n = 80) and ER patients (n = 132), ORR was 60%, 50%, and 66%; with CR/CRu in 36%, 26%, and 31%; respectively. 199 pts (51%) completed 12c of induction R2, and 188 (48%) have been randomized and entered maintenance. 139 pts (35%) prematurely discontinued both lenalidomide and rituximab, primarily due to AEs (n = 52, 13%) or PD (n = 45, 11%). Most common all-grade AEs were 48% fatigue, 43% neutropenia, 36% diarrhea, and 31% nausea. Grade 3/4 AE neutropenia was 36% (9 pts [2%] had febrile neutropenia); all other grade 3/4 AEs occurred in <7% of pts. Discussion: R2 is active with a tolerable safety profile in pts with R/R FL and MZL, including R-ref, double-ref, and ER pts. Conclusions: These results suggest that R2 should be considered as a therapeutic option for pts with R/R iNHL.