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The challenges of checkpoint inhibition in the treatment of multiple myeloma

机译：检查点抑制治疗多发性骨髓瘤的挑战

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摘要

Despite significant improvements in the overall survival of patients with multiple myeloma (MM) over the past 15 years, the disease remains incurable. Treatment options are limited for patients who have relapsed or are refractory to immunomodulatory drugs (IMiDs), proteasome inhibitors, and monoclonal antibodies. In these patients, immunotherapies such as checkpoint inhibitors, oncolytic vaccines, and chimeric antigen receptor (CAR) T cells provide a potentially effective alternative treatment. While checkpoint inhibitors are effective in prolonging overall survival in some patients with advanced solid cancers and Hodgkin lymphoma, they have not demonstrated significant activity as a single agent in MM. In fact the combination of checkpoint inhibitors with IMiDs was recently found to increase the risk of death in myeloma patients. These challenges highlight the need for a better understanding of immune dysregulation in myeloma patients, and the mechanisms of action of- and resistance to-checkpoint inhibitors. In this review, we summarize immune dysfunction in patients with MM, and review the preclinical and clinical data regarding checkpoint inhibitors in myeloma. We conclude by proposing strategies to improve the efficacy and safety of checkpoint inhibitors in this population.
机译：尽管在过去的15年里，患有多种骨髓瘤（MM）患者的整体存活率显着改善，但该疾病仍然是可行的。对已复发或难治于免疫调节药物（IMID），蛋白酶体抑制剂和单克隆抗体的患者有限的治疗选择有限。在这些患者中，诸如检查点抑制剂，溶瘤疫苗和嵌合抗原受体（CAR）T细胞等免疫疗法提供了潜在有效的替代处理。虽然检查点抑制剂在一些先进的固体癌症和霍格金淋巴瘤延长的患者中延长整体生存期时，它们尚未将显着的活性作为单一剂量的MM。实际上，最近发现含有IMID的检查点抑制剂的组合增加了骨髓瘤患者死亡风险。这些挑战突出了对骨髓瘤患者的免疫失调的需要，以及对检查点抑制剂的作用机制。在本综述中，我们总结了MM患者的免疫功能障碍，并回顾了关于骨髓瘤检查点抑制剂的临床前和临床数据。我们通过提出改善该人群检查点抑制剂的疗效和安全性的策略来结束。

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