MedStar Georgetown University/Washington Hospital Center.
Georgetown University.
J Immunother. 2018 Sep;41(7):332-335. doi: 10.1097/CJI.0000000000000239.
The immune checkpoint inhibitors have brought about a paradigm shift in the treatment of many cancers and are being used as the first line therapy in increasing number of aggressive malignancies, including metastatic melanoma. Their adverse effects, mostly mediated by an uncontrolled overactivation of the immune system, may compromise the therapeutic benefit. Combination immune checkpoint therapies in particular, have higher therapeutic efficacy, but have also been associated with a higher incidence of severe immune-related adverse effects including autoimmune lymphocytic myocarditis. Recent clinical reports of this rare and life threatening condition indicated rapid progression of severe hemodynamic and electrical instability, with or without acute decompensated heart failure, reduced ejection fraction and shock, pointing to the need for early recognition, diagnosis and prompt management. Current guidelines for management of other immune-related adverse effects recommend high-dose glucocorticoids, with consideration of immunomodulators, such as infliximab in patients with severe colitis. However, knowledge about the treatment approaches in immune-related myocarditis remains extremely scarce. Here we report a case of severe, steroid refractory, lymphocytic myocarditis that occurred after the first cycle of combination immunotherapy with the programmed cell death protein-1 inhibitor, nivolumab, and the cytotoxic T-lymphocyte-associated protein 4 blocker, ipilimumab, for metastatic melanoma. We discuss treatment approaches including the role for transvenous pacemaker, advanced heart failure support, and interdisciplinary decision making.
免疫检查点抑制剂在许多癌症的治疗中带来了范式转变,并且在越来越多的侵袭性恶性肿瘤中被用作一线治疗,包括转移性黑色素瘤。它们的不良反应主要是由免疫系统的不受控制的过度激活引起的,可能会影响治疗效果。特别是联合免疫检查点治疗具有更高的治疗效果,但也与更高的严重免疫相关不良反应发生率相关,包括自身免疫性淋巴细胞性心肌炎。最近关于这种罕见且危及生命的疾病的临床报告表明,严重的血液动力学和电不稳定迅速进展,伴有或不伴有急性失代偿性心力衰竭、射血分数降低和休克,这表明需要早期识别、诊断和及时治疗。目前其他免疫相关不良反应的管理指南建议对严重结肠炎患者使用高剂量糖皮质激素,并考虑使用免疫调节剂,如英夫利昔单抗。然而,关于免疫相关性心肌炎的治疗方法的知识仍然非常匮乏。在这里,我们报告了一例严重的、类固醇难治性淋巴细胞性心肌炎的病例,该病例发生在转移性黑色素瘤的第一周期联合免疫治疗后,使用程序性细胞死亡蛋白-1 抑制剂nivolumab 和细胞毒性 T 淋巴细胞相关蛋白 4 阻断剂 ipilimumab。我们讨论了治疗方法,包括经静脉起搏器的作用、晚期心力衰竭支持和跨学科决策。