Sehn Laurie H, Bartlett Nancy L, Matasar Matthew J, Schuster Stephen J, Assouline Sarit E, Giri Pratyush, Kuruvilla John, Shadman Mazyar, Cheah Chan Yoon, Dietrich Sascha, Fay Keith, Ku Matthew, Nastoupil Loretta J, Wei Michael C, Yin Shen, To Iris, Kaufman Derrick, Kwan Antonia, Penuel Elicia, Bolen Christopher R, Budde Lihua E
Department of Medical Oncology, BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, BC, Canada.
Division of Oncology, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO.
Blood. 2025 Feb 13;145(7):708-719. doi: 10.1182/blood.2024025454.
Mosunetuzumab, a CD20×CD3 T-cell engaging bispecific antibody, redirects T cells to eliminate malignant B cells. We present updated efficacy and safety data of a pivotal phase 1/2 study after a median follow-up of 37.4 months in 90 patients with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior lines of therapy treated with fixed-duration mosunetuzumab. Investigator-assessed complete response (CR) rate and objective response rate were 60.0% (95% confidence interval [CI], 49.1-70.2) and 77.8% (95% CI, 67.8-85.9), respectively. Among 70 responders, median duration of response was 35.9 months (95% CI, 20.7 to not estimable [NE]). Among 54 patients who achieved CR, 49 remained in CR at the end of treatment; median duration of CR was not reached (NR; 95% CI, 33.0 to NE); Kaplan-Meier-estimated 30-month remission rate was 72.4% (95% CI, 59.2-85.6). Estimated 36-month overall survival (OS) rate was 82.4% (95% CI, 73.8-91.0); median OS was NR (95% CI, NE to NE). Median progression-free survival was 24.0 months (95% CI, 12.0 to NE). Median time to CD19+ B-cell recovery was 18.4 months (95% CI, 12.8-25.0) after 8 cycles of mosunetuzumab treatment. No new cytokine release syndrome events or fatal, serious, or grade ≥3 adverse events were reported. With extended follow-up, mosunetuzumab demonstrated high response rates, durable remissions, and manageable safety with no long-term concerns. This supports outpatient mosunetuzumab administration as an off-the-shelf, fixed-duration, safe, and effective treatment for patients with R/R FL, including those with high-risk disease. This trial was registered at www.clinicaltrials.gov as #NCT02500407.
莫苏奈妥珠单抗是一种靶向 CD20×CD3 的双特异性 T 细胞衔接抗体，可重定向 T 细胞以消除恶性 B 细胞。我们公布了一项关键 1/2 期研究的最新疗效和安全性数据，该研究对 90 例复发/难治性（R/R）滤泡性淋巴瘤（FL）患者进行了为期 37.4 个月的中位随访，这些患者既往接受过≥2 线治疗且接受了固定疗程的莫苏奈妥珠单抗治疗。研究者评估的完全缓解（CR）率和客观缓解率分别为 60.0%（95%置信区间[CI]，49.1-70.2）和 77.8%（95%CI，67.8-85.9）。在 70 例缓解者中，中位缓解持续时间为 35.9 个月（95%CI，20.7 至不可估计[NE]）。在 54 例达到 CR 的患者中，49 例在治疗结束时仍处于 CR 状态；CR 的中位持续时间未达到（NR；95%CI，33.0 至 NE）；采用 Kaplan-Meier 法估计的 30 个月缓解率为 72.4%（95%CI，59.2-85.6）。估计的 36 个月总生存率（OS）为 82.4%（95%CI，73.8-91.0）；中位 OS 未达到（95%CI，NE 至 NE）。中位无进展生存期为 24.0 个月（95%CI，12.0 至 NE）。在接受 8 个周期的莫苏奈妥珠单抗治疗后，CD19+B 细胞恢复的中位时间为 18.4 个月（95%CI，12.8-25.0）。未报告新的细胞因子释放综合征事件或致命、严重或≥3 级不良事件。随着随访时间的延长，莫苏奈妥珠单抗显示出高缓解率、持久缓解以及可控的安全性，且无长期担忧。这支持将莫苏奈妥珠单抗门诊给药作为一种现成的、固定疗程、安全有效的治疗方法，用于 R/R FL 患者，包括那些患有高危疾病的患者。该试验已在 www.clinicaltrials.gov 上注册，注册号为#NCT02500407。
