Wenming Chen, Chengcheng Fu, Baijun Fang, Aibin Liang, Zhongjun Xia, Yanjuan He, Jin Lu, Hui Liu, Ming Hou, Zhen Cai, Wei Yang, Siguo Hao, Songfu Jiang, Hongmei Jing, Jing Liu, Xin Du, Rong Fu, Heng Mei, Zunmin Zhu, Yanli Yang, Hong Liu, Xingxing Meng, Nishanthan Rajakumaraswamy, Daijing Yuan, Huamao Wang, Zonghai Li
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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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Zevor-cel induces deep and durable responses in heavily pre-treated RRMM patients with a manageable safety profile.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"119"},"PeriodicalIF":13.5000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482220/pdf/","citationCount":"0","resultStr":"{\"title\":\"Phase II study of zevorcabtagene autoleucel, a fully human BCMA-targeting CAR T cell therapy, in patients with relapsed/refractory multiple myeloma.\",\"authors\":\"Wenming Chen, Chengcheng Fu, Baijun Fang, Aibin Liang, Zhongjun Xia, Yanjuan He, Jin Lu, Hui Liu, Ming Hou, Zhen Cai, Wei Yang, Siguo Hao, Songfu Jiang, Hongmei Jing, Jing Liu, Xin Du, Rong Fu, Heng Mei, Zunmin Zhu, Yanli Yang, Hong Liu, Xingxing Meng, Nishanthan Rajakumaraswamy, Daijing Yuan, Huamao Wang, Zonghai Li\",\"doi\":\"10.1186/s40164-025-00710-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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. 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引用次数: 0
摘要
背景：Zevorcabtagene autoleucel （zevor- cell）是一种靶向b细胞成熟抗原的全人自体CAR - t细胞疗法，于2024年在中国获批用于复发/难治性多发性骨髓瘤（RRMM）患者。方法：LUMMICAR STUDY 1是一项在中国23个中心进行的2期单臂研究。年龄≥18岁至≤75岁的RRMM患者，可测量疾病，既往接受≥3条治疗线，器官功能和骨髓储备充足，东部肿瘤合作组（ECOG）评分为0-1，符合条件。先前接受过任何CAR - t细胞治疗或任何bcma定向治疗的患者不符合条件。主要终点是由独立审查委员会确定的客观缓解率（ORR）。次要终点包括研究者确定的ORR，其他疗效终点包括完全缓解(CR)/严格完全缓解（sCR）率，反应持续时间（DOR），最小残留疾病阴性，安全性终点包括不良事件的发生率和严重程度，以及零祖细胞的药代动力学。结果：总体而言，125例患者接受了单采，105例患者接受了淋巴细胞清除，102例患者（中位年龄59.5岁[范围：38,75]岁，男性53.9%，女性46.1%）接受了零细胞治疗。ORR为92.2% (95% CI 85.13-96.55)，其中70例（68.6%）患者达到sCR， 3例（2.9%）患者达到CR。在中位随访20.3个月（四分位间距[IQR] 12.5, 23.8）个月时，观察到45例（44.1%）无进展生存期（PFS）事件和20例（19.6%）总生存期（OS）事件，DOR、PFS和OS数据不成熟。92例（90.2%）患者报告细胞因子释放综合征，7例（6.9%）患者报告3级或4级事件。免疫效应细胞相关神经毒性综合征2例，1级；无零灶细胞相关≥3级神经毒性发生。结论：Zevor-cel在大量预处理的RRMM患者中诱导深度和持久的反应，具有可管理的安全性。
Phase II study of zevorcabtagene autoleucel, a fully human BCMA-targeting CAR T cell therapy, in patients with relapsed/refractory multiple myeloma.
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.
期刊介绍：
Experimental Hematology & Oncology is an open access journal that encompasses all aspects of hematology and oncology with an emphasis on preclinical, basic, patient-oriented and translational research. The journal acts as an international platform for sharing laboratory findings in these areas and makes a deliberate effort to publish clinical trials with 'negative' results and basic science studies with provocative findings.
Experimental Hematology & Oncology publishes original work, hypothesis, commentaries and timely reviews. With open access and rapid turnaround time from submission to publication, the journal strives to be a hub for disseminating new knowledge and discussing controversial topics for both basic scientists and busy clinicians in the closely related fields of hematology and oncology.
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