Department of Biochemistry, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia.
Department of Medicine, College of Health Science, Debre Tabor University, Debre Tabor, Ethiopia.
Front Immunol. 2022 Sep 2;13:991092. doi: 10.3389/fimmu.2022.991092. eCollection 2022.
Ciltacabtagene autoleucel (also known as cilta-cel) is a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) on the surface of cancer cells in B cell malignancies, such as multiple myeloma (MM). It is a second-generation CAR that is outfitted with an ectodomain comprising two BCMA-binding single chain variable fragment (ScFv) domains, a transmembrane domain, and an endodomain possessing CD3ζ and 4-1BB. Cilta-cel is an autologous, gene-edited CAR T-cell that is prepared by collecting and modifying the recipient's T-cells to create a patient personalized treatment in the laboratory to be infused back. This CAR T-cell product exceptionally entails CARs with two BCMA-targeting single-domain antibodies that detect two epitopes of BCMA expressed on the malignant cells of MM. Cilta-cel is the current addition to the treatment armamentarium of relapsed or refractory (r/r) MM after its approval by the FDA on February 28, 2022, based on the results of the Phase 1b/2 CARTITUDE-1 study. It was the second approved anti-BCMA CAR T-cell product after idecabtagene vicleucel (ide-cel) to treat myeloma patients. It induces early, deep, and long-lasting responses with a tolerable safety profile in r/r MM. Cilta-cel-treated myeloma patients may potentially experience adverse effects ranging from mild to life-threatening, but they are mostly manageable toxicities. Besides, it has a consistent safety profile upon a longer follow-up of patients. Cilta-cel generally outperforms ide cel in terms of efficacy in MM, but shows comparable adverse events. This review highlights the current updates on cilta-cel efficacy, adverse events, comparison with ide-cel, and its future direction in the treatment of MM.
西达基奥仑赛(又称 cilta-cel)是一种嵌合抗原受体(CAR)T 细胞疗法,针对 B 细胞恶性肿瘤(如多发性骨髓瘤[MM])癌细胞表面的 B 细胞成熟抗原(BCMA)。它是一种第二代 CAR,配备了由两个 BCMA 结合单链可变片段(ScFv)结构域、一个跨膜结构域和一个具有 CD3ζ 和 4-1BB 的内域组成的外显子。Cilta-cel 是一种自体基因编辑的 CAR T 细胞,通过收集和修饰受者的 T 细胞在实验室中制备,以创建个性化的患者治疗方案,然后回输。这种 CAR T 细胞产品特别需要具有两个靶向 BCMA 的单域抗体的 CAR,以检测 MM 恶性细胞上表达的两个 BCMA 表位。Cilta-cel 于 2022 年 2 月 28 日获得 FDA 批准,是 r/r MM 治疗武器库的新增成员,基于 CARTITUDE-1 研究的 1b/2 期结果。它是继 idecabtagene vicleucel(ide-cel)之后第二种批准用于治疗骨髓瘤患者的抗 BCMA CAR T 细胞产品。它在 r/r MM 中具有可耐受的安全性特征,可诱导早期、深度和持久的反应。接受 cilta-cel 治疗的骨髓瘤患者可能会出现从轻度到危及生命的不良反应,但大多数都是可管理的毒性。此外,在对患者进行更长时间的随访后,它具有一致的安全性特征。在 MM 方面,ciltacel 在疗效方面普遍优于 ide-cel,但显示出可比的不良事件。本综述重点介绍了 cilta-cel 在疗效、不良事件、与 ide-cel 的比较以及在 MM 治疗中的未来方向方面的最新进展。
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