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西达基奥仑赛:用于治疗复发或难治性多发性骨髓瘤的第二款抗 BCMA CAR-T 细胞治疗武器。

Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma.

机构信息

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.

出版信息

Front Immunol. 2022 Sep 2;13:991092. doi: 10.3389/fimmu.2022.991092. eCollection 2022.


DOI:10.3389/fimmu.2022.991092
PMID:36119032
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9479060/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/091c/9479060/37ccbd8b73c1/fimmu-13-991092-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/091c/9479060/5759a7f80565/fimmu-13-991092-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/091c/9479060/1355feb562bd/fimmu-13-991092-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/091c/9479060/37ccbd8b73c1/fimmu-13-991092-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/091c/9479060/5759a7f80565/fimmu-13-991092-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/091c/9479060/1355feb562bd/fimmu-13-991092-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/091c/9479060/37ccbd8b73c1/fimmu-13-991092-g003.jpg

相似文献

[1]
Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma.

Front Immunol. 2022

[2]
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Expert Opin Biol Ther. 2024-5

[3]
Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study.

Lancet. 2021-7-24

[4]
Comparison of Cilta-cel, an Anti-BCMA CAR-T Cell Therapy, Versus Conventional Treatment in Patients With Relapsed/Refractory Multiple Myeloma.

Clin Lymphoma Myeloma Leuk. 2022-5

[5]
Matching-adjusted indirect comparison of efficacy outcomes for ciltacabtagene autoleucel in CARTITUDE-1 versus idecabtagene vicleucel in KarMMa for the treatment of patients with relapsed or refractory multiple myeloma.

Curr Med Res Opin. 2021-10

[6]
Chimeric Antigen Receptor T Cell Therapy for Myeloma: Where Are We Now and What Is Needed to Move Chimeric Antigen Receptor T Cells Forward to Earlier Lines of Therapy? Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy.

Transplant Cell Ther. 2024-1

[7]
Ciltacabtagene autoleucel in patients with relapsed/refractory multiple myeloma: CARTITUDE-1 (phase 2) Japanese cohort.

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[8]
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[9]
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[10]
Plain language summary of the CARTITUDE-4 study of ciltacabtagene autoleucel for the treatment of people with relapsed or refractory multiple myeloma.

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[4]
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[5]
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[6]
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[7]
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[10]
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本文引用的文献

[1]
Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies.

Blood Cancer J. 2022-2-24

[2]
Matching-adjusted indirect comparison of efficacy outcomes for ciltacabtagene autoleucel in CARTITUDE-1 versus idecabtagene vicleucel in KarMMa for the treatment of patients with relapsed or refractory multiple myeloma.

Curr Med Res Opin. 2021-10

[3]
Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study.

Lancet. 2021-7-24

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Blood Cancer J. 2021-6-18

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CAR T-cell therapy in multiple myeloma: more room for improvement.

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N Engl J Med. 2021-2-25

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J Clin Oncol. 2021-3-1

[9]
Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma.

J Hematol Oncol. 2020-12-3

[10]
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EBioMedicine. 2020-8

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