Background: Immunomodulation with lenalidomide (L) + rituximab (R) is a promising treatment approach for patients (pts) with indolent NHL. In indolent NHL, frontline L+R provided a 90% overall response rate (ORR) and 64% complete response/complete response unconfirmed (CR/CRu) (Fowler, ASH, 2012). In phase 2 trials of L+R in relapsed/refractory (R/R) disease, pts with mantle-cell lymphoma (MCL) achieved 57% ORR and 36% CR (Wang, Lancet Oncol, 2012); pts with follicular lymphoma (FL) treated with L+R had a higher response rate (73% ORR, 36% CR) compared with those receiving L alone (51% ORR, 13% CR; Leonard, ASCO, oral presentation, 2012). Methods: The phase 3b MAGNIFY study will compare the efficacy and safety of 12 cycles of combination L+R for induction with randomization to L+R (Arm A) vs R (Arm B) maintenance in pts with R/R FL, MCL, or marginal zone lymphoma (MZL). Target enrollment is ~500. Pts will be randomized 1:1 to 28-day (d) treatment cycles. In both arms, pts will receive induction L (20 mg/d on d 1-21; 12 cycles) + R (375 mg/m² on d 1, 8, 15, 22 in cycle 1; d1 of cycles 3, 5, 7, 9, 11). In Arm A, pts will receive maintenance L (10 mg/d on d 1-21; cycles 13-30) + R (375 mg/m² on d1 of every other cycle from 13-29), followed by L (10 mg/d on d 1-21) until progression. Following 12 cycles of induction with L+R, pts in Arm B will receive maintenance R (375 mg/m² on d1 of every other cycle from 13- 29). Eligible pts must have R/R grade 1, 2, or 3a FL, MZL, or MCL; have completed previous systemic therapy; have ≥1 measurable lesion; and have adequate bone marrow, liver, and renal function (moderate renal impairment acceptable). The primary endpoint is progression-free survival. Key secondary endpoints include rate of CR/CRu, overall survival, ORR, duration of response, duration of CR/CRu, and safety. Health-related quality of life, as measured by the FACT-Lym questionnaire, will be assessed as an exploratory endpoint. This trial is currently enrolling pts. Clinical trial information: NCT01996865.