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治疗皮肤 T 细胞淋巴瘤(CTCL)的研究性药物:最新进展。

Investigative drugs for the treatment of cutaneous T-cell lymphomas (CTCL): an update.

机构信息

Department of Dermatology, University Hospital of Zurich , Zurich , Switzerland.

Faculty of Medicine, University of Zurich , Zurich , Switzerland.

出版信息

Expert Opin Investig Drugs. 2019 Sep;28(9):799-809. doi: 10.1080/13543784.2019.1654995. Epub 2019 Aug 18.

Abstract

: Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms, which represent approximately 75% of all primary cutaneous lymphomas. Mycosis fungoides and Sézary syndrome are the most common CTCL. Early stage disease follows a protracted course, carries a 5-year disease specific survival of 97% and can be treated with skin-directed therapies. Widespread, advanced disease has a 5-year OS of less than 25% and necessitates systemic treatment. Allogeneic stem cell transplantation is a potentially curative treatment option for advanced CTCL, however, transplant-related morbidity and mortality must be considered and a risk-benefit assessment performed on individual basis. : Herein, we provide a review of investigative drugs in early-stage trials for the treatment of cutaneous CTCL, including topically applied immunomodulators such as replicating herpes virus or toll-like receptor 7/8 agonist resiquimod and systemic therapies with monoclonal antibodies, such as anti-CD47, recombinant cytotoxic interleukin 2 fusion protein anti-KIR3DL2 antibody and anti-miR-155 antibody. n: Among the reviewed drugs, resiquimod shows promising clinical efficacy with good tolerability in early CTCL. In refractory or relapsed disease, intratumoral anti-CD47-, anti-CCR4- and anti-KIR3DL2-antibodies show high response rates, however, latter two also show considerable toxicity. Larger trials are needed to better evaluate the discussed therapies.

摘要

: 皮肤 T 细胞淋巴瘤(CTCL)是一组异质性的皮肤归巢 T 细胞肿瘤,约占所有原发性皮肤淋巴瘤的 75%。蕈样真菌病和赛泽里综合征是最常见的 CTCL。早期疾病呈慢性进展,5 年疾病特异性生存率为 97%,可采用皮肤靶向治疗。广泛的晚期疾病 5 年 OS 低于 25%,需要全身治疗。异基因造血干细胞移植是晚期 CTCL 潜在的治愈性治疗选择,但必须考虑移植相关发病率和死亡率,并根据个体情况进行风险获益评估。: 本文综述了早期 CTCL 治疗的临床试验中的研究药物,包括局部应用免疫调节剂,如复制型疱疹病毒或 Toll 样受体 7/8 激动剂瑞喹莫德,以及单克隆抗体的系统治疗,如抗 CD47、重组细胞毒性白细胞介素 2 融合蛋白抗 KIR3DL2 抗体和抗 miR-155 抗体。: 在回顾的药物中,瑞喹莫德在早期 CTCL 中具有良好的耐受性和有前景的临床疗效。在难治性或复发性疾病中,肿瘤内抗 CD47、抗 CCR4 和抗 KIR3DL2 抗体显示出高缓解率,但后两者也表现出相当大的毒性。需要更大规模的试验来更好地评估所讨论的治疗方法。

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