New therapeutic perspectives to manage refractory immune checkpoint-related toxicities
New therapeutic perspectives to manage refractory immune checkpoint-related toxicities
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DOI：
10.1016/s1470-2045(18)30828-3
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发表时间：
2019-01-01
期刊：
影响因子：
51.1
通讯作者：
Obeid, Michel
中科院分区：
文献类型：
--
作者：
Martins, Filipe;Sykiotis, Gerasimos P.;Obeid, Michel
免疫检查点抑制剂正在重塑许多癌症的预后，并逐渐成为许多肿瘤类型治疗的标准护理。免疫疗法给患者带来了新的希望，但也给医疗从业者带来了全新的毒性。参与癌症患者多学科管理的肿瘤学家和专家越来越多地面临着治疗严重和难治性免疫相关不良事件患者的治疗挑战。在本个人观点中，我们总结了用于管理免疫检查点抑制剂治疗引起的此类毒性的治疗策略。根据目前对其发病机制的了解，我们讨论了使用新的生物和非生物免疫抑制药物来治疗严重和类固醇难治性免疫相关不良事件。根据主要的免疫浸润类型，我们提出了一种超越典型皮质类固醇使用的个性化管理治疗算法。我们提出了一种所谓的关闭策略，旨在抑制参与免疫相关不良事件病理生理过程的关键炎症成分，并限制药物免疫抑制对肿瘤反应的潜在不良影响。这种方法是在当前指南的基础上发展起来的，并对药物免疫抑制的逐步增加方法提出了挑战。
Immune checkpoint inhibitors are reshaping the prognosis of many cancer and are progressively becoming the standard of care in the treatment of many tumour types. Immunotherapy is bringing new hope to patients, but also a whole new spectrum of toxicities for healthcare practitioners to manage. Oncologists and specialists involved in the pluridisciplinary management of patients with cancer are increasingly confronted with the therapeutic challenge of treating patients with severe and refractory immune-related adverse events. In this Personal View, we summarise the therapeutic strategies that have been used to manage such toxicities resulting from immune checkpoint inhibitor treatment. On the basis of current knowledge about their pathogenesis, we discuss the use of new biological and non-biological immunosuppressive drugs to treat severe and steroid refractory immune-related adverse events. Depending on the immune infiltrate type that is predominant, we propose a treatment algorithm for personalised management that goes beyond typical corticosteroid use. We propose a so-called shut-off strategy that aims at inhibiting key inflammatory components involved in the pathophysiological processes of immune-related adverse events, and limits potential adverse effects of drug immunosuppression on tumour response. This approach develops on current guidelines and challenges the step-by-step increase approach to drug immunosuppression.