AbstractRelapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) is generally considered incurable with current treatment options. Previous phase 1b/2 results showed combining the anti–cluster-of-differentiation 47 (CD47) activity of magrolimab with the anti-CD20 activity of rituximab (M + R) has antitumor activity against R/R iNHL. Here, we report 3-year follow-up data from this phase 1b/2 study assessing long-term safety and efficacy of M + R in R/R iNHL. After magrolimab priming, 4 groups of patients in phase 1b M + R received 10 to 45 mg/kg magrolimab maintenance doses with 375 mg/m2 rituximab. Phase 2 explored 30 and 45 mg/kg magrolimab. Primary end points were treatment-emergent adverse events (TEAEs) and objective response rate (ORR). Secondary end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Exploratory analysis included assessment of circulating tumor DNA, biomarkers of magrolimab tumor penetration, and drug target expression. Of 46 patients treated in phase 1b/2, 42 had follicular lymphoma and 4 had marginal zone lymphoma. All patients experienced ≥1 any-grade TEAE, and 44 reported ≥1 treatment-related TEAE. No additional toxicities were reported during long-term follow-up, and there were no treatment-related deaths. Median follow-up was 36.7 (range, 1.2-62.3) months. The ORR was 52.2%, with 30.4% achieving a complete response. The median DOR was 15.9 (95% confidence interval [CI], 5.6 to not estimable) months. The median time-to-response was 1.8 (range, 1.6-5.5) months; median PFS and OS were 7.4 (95% CI, 4.8-13.0) months and not reached, respectively. These results demonstrate the long-term safety and efficacy of M + R in patients with iNHL and support further exploration of CD47-based treatment combinations. This trial was registered at www.ClinicalTrials.gov as #NCT02953509.