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免疫检查点抑制剂在合并HIV感染的癌症患者中的安全性和有效性:近期进展与未来需求展望

Safety and Efficacy of Immune Checkpoint Inhibitors in Patients With Cancer Living With HIV: A Perspective on Recent Progress and Future Needs.

作者信息

Sahin Ibrahim Halil, Kane Sujata R, Brutcher Edith, Guadagno Jessica, Smith Katherine E, Wu Christina, Lesinski Gregory B, Gunthel Clifford J, El-Rayes Bassel F

机构信息

Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA.

出版信息

JCO Oncol Pract. 2020 Jun;16(6):319-325. doi: 10.1200/JOP.19.00754. Epub 2020 Mar 11.

Abstract

Recent studies have identified durable responses with the use of immune checkpoint inhibitors in patients with mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC). The dramatic improvement in clinical outcomes led to the US Food and Drug Administration approval of pembrolizumab, nivolumab, and nivolumab in combination with ipilimumab in metastatic patients with MSI-H/MMR-D CRC who previously experienced progression on cytotoxic therapies. In the clinical trials investigating these agents, HIV-seropositive patients were not included and therefore the clinical efficacy of these agents in patients with metastatic MSI-H/MMR-D CRC living with HIV is unclear. On the basis of growing evidence, immune checkpoint blockade therapies seem to be a safe approach in patients with well-controlled HIV infection. Research on immunotherapeutic approaches in patients living with HIV and cancer is an area of unmet medical need that can be addressed by clinical trial designs that are inclusive of patients with well-controlled seropositive HIV and trials that specifically evaluate immune therapies in patients living with HIV.

摘要

近期研究已证实,在错配修复缺陷(MMR-D)/微卫星高度不稳定(MSI-H)的转移性结直肠癌(CRC)患者中使用免疫检查点抑制剂可产生持久反应。临床结局的显著改善促使美国食品药品监督管理局批准帕博利珠单抗、纳武利尤单抗以及纳武利尤单抗与伊匹木单抗联合用于先前接受细胞毒性疗法后病情进展的MSI-H/MMR-D转移性CRC患者。在研究这些药物的临床试验中,未纳入HIV血清学阳性患者,因此这些药物在合并HIV的MSI-H/MMR-D转移性CRC患者中的临床疗效尚不清楚。基于越来越多的证据,免疫检查点阻断疗法在HIV感染得到良好控制的患者中似乎是一种安全的方法。对合并HIV和癌症患者的免疫治疗方法的研究是一个尚未满足的医学需求领域,可通过纳入HIV血清学阳性且病情得到良好控制的患者的临床试验设计以及专门评估合并HIV患者免疫疗法的试验来解决。

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