ImportanceEquecabtagene autoleucel (eque-cel), a fully human-derived B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell therapy, has exhibited potential for the treatment of relapsed or refractory multiple myeloma (RRMM), and further investigation in a larger cohort is necessary.ObjectiveTo evaluate whether eque-cel can benefit patients with RRMM and determine the overall response rate postinfusion.Design, Setting, and ParticipantsThe FUMANBA-1 trial was a single-arm, open-label, phase 1b/2 trial that evaluated eque-cel in adult patients with RRMM. Enrollment began in April 2020, and patients who received eque-cel will be monitored for a minimum of 15 years following the infusion. As of September 2022, patients with heavily pretreated RRMM who received at least 3 prior courses of therapy from 14 centers were enrolled. Data were analyzed from April 2020 to September 2022.InterventionsPatients received a single infusion of eque-cel at 1.0 × 106 CAR-positive T cells/kg after the lymphodepletion.Main Outcomes and MeasuresEfficacy was the primary objective, and safety, pharmacokinetics, and pharmacodynamics were secondary objectives.ResultsOf 103 patients who received an eque-cel infusion, 55 (53.4%) were male, and the median (range) age was 58 (39-70) years. A total of 101 patients were evaluable for efficacy. At a median (range) follow-up of 13.8 (0.4-27.2) months, the overall response rate was 96.0% (97 of 101), with 74.3% (75 of 103) achieving a complete response or better. Among the 12 patients who had prior CAR T-cell treatment, 75% (9 of 12) achieved a response. The median progression-free survival was not reached, with a 12-month progression-free survival rate of 78.8% (95% CI, 68.6-86.0). A total of 96 patients (95.0%) achieved minimal residual disease negativity at a sensitivity threshold of 10−5. Adverse events were favorable: 96 of 103 patients (93.2%) experienced cytokine release syndrome (grade 1 to 2 in 95 patients [92.3%]) and 2 (1.9%) experienced immune effector cell–associated neurotoxicity syndrome (grade 1 to 2). All cases of immune effector cell–associated neurotoxicity syndrome and 94 of 96 cases of cytokine release syndrome resolved with treatment. Additionally, only 20 patients (19.4%) developed antidrug antibodies. Cellular kinetic analysis confirmed CAR-positive T cells in all patients, with the longest duration at 735 days.Conclusions and RelevanceIn this trial, eque-cel led to early, deep, and durable responses in patients with heavily pretreated RRMM with a manageable safety profile. Patients with prior CAR T-cell therapy also benefitted from eque-cel.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2000033946

中文翻译：

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Equecabtagene Autoleucel 治疗复发或难治性多发性骨髓瘤患者


重要性Equecabtagene autoleucel （eque-cel） 是一种完全人源 B 细胞成熟抗原靶向嵌合抗原受体 （CAR） 的 T 细胞疗法，已显示出治疗复发或难治性多发性骨髓瘤 （RRMM） 的潜力，有必要在更大的队列中进行进一步研究。目的评价 eque-cel 是否能使 RRMM 患者受益，并确定输注后总体缓解率。设计、环境和参与者FUMANBA-1 试验是一项单臂、开放标签、1b/2 期试验，旨在评估 eque-cel 在成年 RRMM 患者中的疗效。入组于 2020 年 4 月开始，接受 eque-cel 的患者将在输注后接受至少 15 年的监测。截至 2022 年 9 月，纳入了来自 14 个中心至少接受过 3 个既往疗程的 RRMM 患者。干预患者在淋巴细胞耗竭后接受 1.0 × 106 个 CAR 阳性 T 细胞/kg 的单次 eque-cel 输注。主要结局和措施疗效是主要目标，安全性、药代动力学和药效学是次要目标。结果在接受 eque-cel 输注的 103 例患者中，55 例 （53.4%） 为男性，中位 （范围） 年龄为 58 （39-70） 岁。共有 101 例患者进行了疗效评估。在中位 （范围） 随访 13.8 （0.4-27.2） 个月时，总体缓解率为 96.0% （101 例中的 97 例），其中 74.3% （103 例中的 75 例） 达到完全缓解或更好。在既往接受过 CAR T 细胞治疗的 12 例患者中，75% （12 例中的 9 例） 达到反应。未达到中位无进展生存期，12 个月无进展生存率为 78.8% （95% CI，68.6-86.0）。共有 96 名患者 （95.0%） 在 10-5 的敏感性阈值下达到微小残留病阴性。不良事件是有利的：103 例患者中有 96 例 （93.2%） 出现细胞因子释放综合征 （95 例患者中为 1 至 2 级 [92.3%]），2 例 （1.9%） 出现免疫效应细胞相关神经毒性综合征 （1 至 2 级）。所有免疫效应细胞相关神经毒性综合征病例和 94 例细胞因子释放综合征中的 96 例均经治疗消退。此外，只有 20 例患者 （19.4%） 产生抗药抗体。细胞动力学分析证实所有患者均为 CAR 阳性 T 细胞，最长持续时间为 735 天。结论和相关性在这项试验中，eque-cel 在经过大量治疗的 RRMM 患者中产生了早期、深入和持久的反应，且安全性可控。既往接受过 CAR T 细胞治疗的患者也受益于 eque-cel。试验注册Chinese Clinical Trial Registry 标识符： ChiCTR2000033946