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作者信息

Salles Gilles, Sesques Pierre, Ferrant Emmanuelle, Safar Violaine, Ghesquieres Hervé, Bachy Emmanuel

机构信息

Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d'Hématologie, 69495 Pierre Bénite cedex, France; Université Claude Bernard Lyon-1, 69100 Villeurbanne, France.

Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d'Hématologie, 69495 Pierre Bénite cedex, France; Université Claude Bernard Lyon-1, 69100 Villeurbanne, France.

出版信息

Bull Cancer. 2018 Dec;105 Suppl 2:S168-S177. doi: 10.1016/S0007-4551(19)30047-5.

Abstract

After the promising results obtained in North American academic centers suggesting the curative potential of these treatments, the development of T cells carrying a chimeric antigen receptor (CAR-T) directed against the CD19 antigen has experienced rapid developments in recent years. Three major trials (each involving about 100 patients with relapsed or refractory aggressive B-cell lymphoma) were conducted and evaluated the efficacy of these treatments (Zuma-1, Juliet and Transcend). Tumor responses are observed in 52% to 82% of patients, with a best complete response (CR) rate of 40% to 58%. Although some patients with early CR may relapse rapidly, the quality of the response appears to improve over time for other patients in partial response, all of which result in a proportion of patients with prolonged CR by approximately 30% to 40% (up to more than one year after treatment). Toxicities (mostly early and reversible) are mainly represented by the cytokine release syndrome (severe in 1% to 22% of patients) and neurological disorders sometimes severe (in 12% to 31% of patients), while other patients develop cytopenias or hypogammaglobulinemia. The updating of these studies over time and the new developments (in the improvement of their conception and in their use) of the CAR-T will allow to better defining the place of these innovative and promising treatments in the therapeutic strategy of patients with lymphoma. Cet article fait partie du numéro supplément Les cellules CAR-T : une révolution thérapeutique ? réalisé avec le soutien institutionnel des partenaires Gilead : Kite et Celgene.

摘要

在北美学术中心取得的有前景的结果表明这些治疗具有治愈潜力之后,近年来,携带针对CD19抗原的嵌合抗原受体(CAR-T)的T细胞的开发取得了快速进展。进行了三项主要试验(每项试验涉及约100例复发或难治性侵袭性B细胞淋巴瘤患者)并评估了这些治疗的疗效(Zuma-1、Juliet和Transcend)。在52%至82%的患者中观察到肿瘤反应,最佳完全缓解(CR)率为40%至58%。虽然一些早期CR患者可能会迅速复发,但对于其他部分缓解的患者,反应质量似乎会随着时间的推移而改善,所有这些导致一部分患者的CR延长约30%至40%(治疗后长达一年以上)。毒性(大多为早期且可逆)主要表现为细胞因子释放综合征(1%至22%的患者严重)和有时严重的神经系统疾病(12%至31%的患者),而其他患者会出现血细胞减少或低丙种球蛋白血症。随着时间的推移对这些研究的更新以及CAR-T的新进展(在其设计和使用方面的改进)将有助于更好地确定这些创新且有前景的治疗在淋巴瘤患者治疗策略中的地位。本文是在吉利德合作伙伴Kite和新基的机构支持下完成的增刊《CAR-T细胞:一场治疗革命?》的一部分。

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