复发/难治性 (R/R) 惰性非霍奇金淋巴瘤 (iNHL) 通常被认为采用当前的治疗方案无法治愈。先前的 1b/2 期结果显示，将 Magrolimab 的抗分化簇 (CD) 47 活性与利妥昔单抗 (M R) 的抗 CD20 活性相结合，具有针对 R/R iNHL 的抗肿瘤活性。在这里，我们报告了这项 1b/2 期研究 (NCT02953509) 的 3 年随访数据，评估了 M R 在 R/R iNHL 中的长期安全性和有效性。 Magrolimab 启动后，4 组 1b 期 MR 患者接受 10-45 mg/kg Magrolimab 维持剂量和 375 mg/m2 利妥昔单抗。第 2 阶段探索了 30 和 45 mg/kg 的 Magrolimab。主要终点是治疗中出现的不良事件（TEAE）和客观缓解率（ORR）。次要终点包括缓解持续时间（DOR）、无进展生存期（PFS）和总生存期（OS）。探索性分析包括循环肿瘤 DNA、magrolimab 肿瘤渗透生物标志物和药物靶点表达的评估。在 1b/2 期治疗的 46 名患者中，42 名患有滤泡性淋巴瘤，4 名患有边缘区淋巴瘤。所有患者均经历过≥1 次任何级别的 TEAE，其中 44 名患者报告≥1 次与治疗相关的 TEAE。在长期随访期间没有报告其他毒性，也没有与治疗相关的死亡。中位随访时间为 36.7（范围：1.2-62.3）个月。 ORR 为 52.2%，其中 30.4% 达到完全缓解。中位 DOR 为 15.9（95% CI，5.6-不可估计）个月。中位反应时间为 1.8（范围，1.6-5.5）个月；中位 PFS 和 OS 分别为 7.4 (95% CI, 4.8-13.0) 个月，但尚未达到。这些结果证明了 M R 对 iNHL 患者的长期安全性和有效性，并支持进一步探索基于 CD47 的治疗组合。版权所有 © 2024 美国血液学会。

Relapsed/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 (CD) 47 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 (NCT02953509) assessing long-term safety and efficacy of M+R in R/R iNHL. After magrolimab priming, 4 groups of phase 1b M+R patients received 10-45 mg/kg magrolimab maintenance doses with 375 mg/m2 rituximab. Phase 2 explored 30 and 45 mg/kg magrolimab. Primary endpoints were treatment-emergent adverse events (TEAEs) and objective response rate (ORR). Secondary endpoints 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% CI, 5.6-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.Copyright © 2024 American Society of Hematology.