Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy.
Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy.
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DOI：
10.1158/2643-3230.bcd-22-0074
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发表时间：
2023-03-01
影响因子：
11.2
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中科院分区：
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在高危多发性骨髓瘤患者中进行的早期抗BCMA和抗CD 19 CAR T细胞的I期试验证明了双靶点CAR T治疗的安全性和可行性，并将其作为早期治疗进行维持。我们在对三线或更二线治疗有反应的多发性骨髓瘤（MM）患者（A期，N = 10）或对一线治疗有反应的高危患者（B期，N = 20）中进行了一项抗BCMA嵌合抗原受体T细胞（CART-BCMA）联合或不联合抗CD 19 CAR T细胞（huCART 19）的I期临床试验，随后进行了早期来那度胺或泊马度胺维持治疗。我们没有观察到高级别的细胞因子释放综合征（CRS），只有一例低级别的神经毒性。在15例具有可测量疾病的受试者中，10例表现出部分缓解（PR）或更佳;在26例既往治疗有缓解的受试者中，9例改善了其缓解类别，4例转化为微小残留病（MRD）阴性完全缓解/严格完全缓解。早期维持治疗是安全、可行的，并且在一些具有CAR T细胞再扩增和迟发型持久临床应答的患者中是一致的。CART-BCMA + huCART 19的结果与单独的CART-BCMA相似。总的来说，我们的结果证明了双靶点CAR T细胞疗法在MM治疗的早期线中具有良好的安全性、药代动力学和抗骨髓瘤活性。CAR T细胞在MM治疗的早期线可能比在先前研究集中的晚期环境中更安全，更有效。我们评估了CAR T细胞在低疾病负担患者中的安全性、药代动力学和疗效，这些患者对当前治疗有反应，并与标准维持治疗相结合。 这篇文章在本期专题中突出显示，第101页
A Phase I trial of early-line anti-BCMA and anti-CD19 CAR T cells in high-risk multiple myeloma patients demonstrated safety and feasibility of dual-target CAR T therapy with maintenance as an early-line treatment. We conducted a phase I clinical trial of anti-BCMA chimeric antigen receptor T cells (CART-BCMA) with or without anti-CD19 CAR T cells (huCART19) in multiple myeloma (MM) patients responding to third- or later-line therapy (phase A, N = 10) or high-risk patients responding to first-line therapy (phase B, N = 20), followed by early lenalidomide or pomalidomide maintenance. We observed no high-grade cytokine release syndrome (CRS) and only one instance of low-grade neurologic toxicity. Among 15 subjects with measurable disease, 10 exhibited partial response (PR) or better; among 26 subjects responding to prior therapy, 9 improved their response category and 4 converted to minimal residual disease (MRD)–negative complete response/stringent complete response. Early maintenance therapy was safe, feasible, and coincided in some patients with CAR T-cell reexpansion and late-onset, durable clinical response. Outcomes with CART-BCMA + huCART19 were similar to CART-BCMA alone. Collectively, our results demonstrate favorable safety, pharmacokinetics, and antimyeloma activity of dual-target CAR T-cell therapy in early lines of MM treatment. CAR T cells in early lines of MM therapy could be safer and more effective than in the advanced setting, where prior studies have focused. We evaluated the safety, pharmacokinetics, and efficacy of CAR T cells in patients with low disease burden, responding to current therapy, combined with standard maintenance therapy. This article is highlighted in the In This Issue feature, p. 101