肿瘤细胞治疗研究
英文原题：Phase II study of zevorcabtagene autoleucel, a fully human BCMA-targeting CAR T cell therapy, in patients with relapsed/refractory multiple myeloma.
Phase II study of zevorcabtagene autoleucel, a fully human BCMA-targeting CAR T cell therapy, in patients with relapsed/refractory multiple myeloma.
Zevor-cel 在重度经治的复发/难治性多发性骨髓瘤患者中诱导深度且持久的缓解，且安全性可控。
背景：Zevorcabtagene autoleucel（zevor-cel）是一种全人源、自体、靶向B细胞成熟抗原的CAR-T细胞疗法，自2024年起在中国获批用于复发/难治性多发性骨髓瘤（RRMM）。方法：LUMMICAR STUDY 1是一项在中国23个中心开展的II期单臂研究。纳入18至75岁、存在可测量疾病、既往接受过3线治疗、器官功能和骨髓储备充足且ECOG评分为0–1的RRMM患者。既往接受过任何CAR-T或BCMA靶向治疗者不符合条件。主要终点为独立审查委员会评定的客观缓解率（ORR）；次要终点包括研究者评定的ORR、完全缓解（CR）/严格完全缓解（sCR）率、缓解持续时间（DOR）、微小残留病阴性率等疗效指标，不良事件发生率和严重程度等安全性指标，以及zevor-cel药代动力学。结果：125例患者接受单采，105例接受淋巴细胞清除治疗，102例接受zevor-cel；中位年龄59.5岁（范围38–75岁），男性占53.9%，女性占46.1%。ORR为92.2%（95% CI 85.13–96.55），其中70例（68.6%）达到sCR，3例（2.9%）达到CR。中位随访20.3个月（四分位距12.5–23.8个月）时，观察到45例（44.1%）PFS事件和20例（19.6%）OS事件，DOR、PFS和OS数据尚不成熟。92例患者（90.2%）发生细胞因子释放综合征，其中7例（6.9%）为3或4级。2例患者发生1级免疫效应细胞相关神经毒性综合征；未发生与zevor-cel相关的3级神经毒性。结论：Zevor-cel可使经多线治疗的RRMM患者获得深度且持久的应答，安全性可管理。
BACKGROUND: Zevorcabtagene autoleucel (zevor-cel) is a fully human autologous CAR T-cell therapy targeting B-cell maturation antigen approved in China since 2024 for patients with relapsed/refractory multiple myeloma (RRMM). METHODS: LUMMICAR STUDY 1 is a phase 2, single-arm study conducted across 23 centers in China. RRMM patients aged 18 to 75 years with measurable disease who had received 3 prior lines of therapy, with adequate organ function and bone marrow reserve, with an Eastern Cooperative Oncology Group (ECOG) score of 0-1, were eligible. Patients previously treated with any CAR T-cell therapy, or any BCMA-directed therapy were ineligible. The primary endpoint was objective response rate (ORR) determined by an Independent Review Committee. The secondary endpoints included ORR determined by investigator, additional efficacy outcomes including complete response (CR)/ stringent complete response (sCR) rate, duration of response (DOR), minimal residual disease negativity, safety outcomes including incidence and severity of adverse events, and pharmacokinetics of zevor-cel. RESULTS: Overall, 125 patients underwent apheresis, 105 patients received lymphodepletion, 102 patients (median age of 59.5 [range: 38, 75] years; 53.9% male and 46.1% female) received zevor-cel. The ORR was 92.2% (95% CI 85.13-96.55) with 70 patients (68.6%) achieving sCR and 3 (2.9%) achieving CR. At a median follow-up of 20.3 (interquartile range [IQR] 12.5, 23.8) months, 45 (44.1%) progression-free survival (PFS) events and 20 (19.6%) overall survival (OS) events were observed, the DOR, PFS and OS data were not mature. Cytokine release syndrome was reported in 92 (90.2%) patients, with grade 3 or 4 events in 7 (6.9%) patients. Immune effector cell associated neurotoxicity syndrome was reported in 2 patients at grade 1; no zevor-cel-related grade 3 neurotoxicity occurred. CONCLUSION: Zevor-cel induces deep and durable responses in heavily pre-treated RRMM patients with a manageable safety profile.
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