新诊断多发性骨髓瘤的 B 细胞成熟抗原/CD19 双靶向免疫疗法

IF 28.4 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology
Wanting Qiang, Jing Lu, Yanchun Jia, Jia Liu, Jin Liu, Haiyan He, Xiaoxiang Wang, Xiaoqiang Fan, Lina Jin, Qianqi Ruan, Qi Zhang, Lianjun Shen, Lihong Weng, Wei Cao, Wenling Li, Juan Du
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引用次数: 0

摘要

重要性:高危新诊断多发性骨髓瘤(NDMM)患者接受标准治疗后往往疗效不佳,因此需要新型有效的前线疗法来提高临床疗效。GC012F是一种B细胞成熟抗原/CD19双靶点嵌合抗原受体(CAR)T细胞疗法,是在新型FasTCAR平台上开发的。值得注意的是,该疗法作为一线疗法用于符合移植条件的高危 NDMM 患者的情况尚未得到深入探讨:目的:研究 GC012F 对 NDMM 患者的安全性、药代动力学、患者健康和生存结果:在2021年6月28日至2023年6月1日(数据截止日期)期间,患者被纳入这项单臂、开放标签的1期队列研究。所有参与研究的患者均在上海长征医院单个中心接受治疗。疗效评估中的患者至少接受了 3 个月的随访:患者接受2个周期的诱导治疗,然后输注GC012F(1×105细胞/公斤、2×105细胞/公斤或3×105细胞/公斤):主要目的是评估不同剂量水平GC012F的安全性、有效性和药代动力学:结果:在接受GC012F治疗的22名患者中,有6人出现了轻度至中度细胞因子释放综合征(1-2级),没有人出现神经毒性反应。19名患者参加了疗效评估,所有19名患者均表现出严格的完全应答,并达到最小残留病阴性。不同剂量水平的治疗效果一致。GC012F显示出快速的反应,首次严格完全反应的中位时间为84天(范围为26-267天),并在28天(范围为23-135天)内达到最小残留疾病阴性。CAR T细胞扩增很强,中位峰值拷贝数为60 652拷贝/μg基因组DNA(范围为8754-331 159拷贝/μg基因组DNA),达到中位峰值拷贝数的中位时间为10天(范围为9-14天):这项单臂、开放标签的1期队列研究结果表明,GC012F可能是一种安全的治疗方法,对符合移植条件的高风险NDMM患者具有积极的健康和生存效果。由于样本量较小,还需要进行更大规模的队列研究和更长时间的随访。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
B-Cell Maturation Antigen/CD19 Dual-Targeting Immunotherapy in Newly Diagnosed Multiple Myeloma.

Importance: Patients with high-risk newly diagnosed multiple myeloma (NDMM) often have poor outcomes with standard treatments, necessitating novel effective frontline therapies to enhance clinical outcomes. GC012F, a B-cell maturation antigen/CD19 dual-targeting chimeric antigen receptor (CAR) T-cell therapy, has been developed on the novel FasTCAR platform. Notably, its use as a frontline therapy for patients with high-risk NDMM who are eligible for transplant has not been thoroughly explored.

Objective: To examine the safety, pharmacokinetics, and patient health and survival outcomes associated with GC012F in individuals with NDMM.

Design, setting, and participants: Patients were enrolled in this single-arm, open-label phase 1 cohort study between June 28, 2021, and June 1, 2023 (the data cutoff date). All patients included in this study were treated at a single center, Shanghai Changzheng Hospital. The patients in the efficacy evaluation were followed up for a minimum period of 3 months.

Intervention: Patients underwent 2 cycles of induction therapy, followed by GC012F infusion (at 1 × 105 cells/kg, 2 × 105 cells/kg, or 3 × 105 cells/kg).

Main outcomes and measures: The primary goals were to assess the safety, efficacy, and pharmacokinetics of GC012F at various dose levels.

Results: Of 22 patients receiving GC012F treatment, 6 experienced mild to moderate cytokine release syndrome (grade 1-2) and none experienced neurotoxic effects. Nineteen patients were included in the efficacy evaluation, and all 19 patients showed stringent complete responses and achieved minimal residual disease negativity. The treatment's effectiveness was consistent across different dose levels. GC012F demonstrated a rapid response, with a median time to first stringent complete response of 84 days (range, 26-267 days) and achieving minimal residual disease negativity within 28 days (range, 23-135 days). The CAR T-cell expansion was robust, with a median peak copy number of 60 652 copies/μg genomic DNA (range, 8754-331 159 copies/μg genomic DNA), and the median time to median peak copy number was 10 days (range, 9-14 days).

Conclusions and relevance: The findings of this single-arm, open-label phase 1 cohort study suggest that GC012F may be a safe treatment associated with positive health and survival outcomes for patients with high-risk NDMM eligible for transplant. Owing to the small sample size, further studies with larger cohorts and longer follow-up durations are needed.

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来源期刊
Jama Oncology
Jama Oncology Medicine-Oncology
CiteScore
37.50
自引率
1.80%
发文量
423
期刊介绍: At JAMA Oncology, our primary goal is to contribute to the advancement of oncology research and enhance patient care. As a leading journal in the field, we strive to publish influential original research, opinions, and reviews that push the boundaries of oncology science. Our mission is to serve as the definitive resource for scientists, clinicians, and trainees in oncology globally. Through our innovative and timely scientific and educational content, we aim to provide a comprehensive understanding of cancer pathogenesis and the latest treatment advancements to our readers. We are dedicated to effectively disseminating the findings of significant clinical research, major scientific breakthroughs, actionable discoveries, and state-of-the-art treatment pathways to the oncology community. Our ultimate objective is to facilitate the translation of new knowledge into tangible clinical benefits for individuals living with and surviving cancer.
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