Department of Urology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho. Kita-gun, Kagawa, 761-0793, Japan.
Department of CardioRenal and CerebroVascular Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
J Med Case Rep. 2021 Oct 15;15(1):508. doi: 10.1186/s13256-021-03097-6.
Immune checkpoint inhibitors are new immunotherapy drugs globally used for many malignancies, including renal cell carcinoma. Myocarditis as an immune-related adverse event is rare but highly fatal, suggesting that its frequency may be higher than reported. This paper describes a case of myocarditis that developed asymptomatically following ipilimumab and nivolumab combination therapy for renal cell carcinoma.
A 71-year-old Asian man who presented to hospital with fever, fatigue, and weight loss of approximately 10 kg within 2 months was diagnosed with Xp.11.2 translocation renal cell carcinoma. Computed tomography revealed multiple lung masses, mediastinal lymph node enlargement, and a level II tumor thrombus reaching the inferior vena cava (cT3bN0M1; International Metastatic Renal Cell Carcinoma Database Consortium, poor risk). Ipilimumab/nivolumab combination therapy was started as induction therapy. The patient experienced acute interstitial nephritis as an immune-related adverse event after treatment initiation; however, a good response to steroid therapy was observed. The antitumor effect of the immunotherapy was notable. Although he experienced pulmonary embolism, it seemed asymptomatic and harmless; thus, a second infusion was introduced. From the eighth day, he demonstrated rapidly worsening cardiogenic shock with asymptomatic electrocardiographic changes and drastic drop in cardiac biomarkers, and a diagnosis of myocarditis as an immune-related adverse event was made. Although immediate methylprednisolone mini-pulse therapy followed by tapered prednisolone prevented mortality, extensive myocardial fibrosis with marked ejection fraction decline persisted as a sequela. Consequently, follow-up without treatment was instituted; however, much of the tumor response initially observed was maintained over several months.
Physicians treating patients with immune checkpoint inhibitors should be aware of their potentially life-threatening cardiotoxic effects. This study emphasized the importance of a high index of suspicion, prompt diagnosis, and early intervention in patients who present with cardiac abnormalities and possible myocarditis after receiving immunotherapy.
免疫检查点抑制剂是全球用于多种恶性肿瘤（包括肾细胞癌）的新型免疫治疗药物。心肌炎作为一种免疫相关的不良反应较为罕见，但具有高度致命性，这表明其发生率可能高于报告的发生率。本文描述了一例肾细胞癌患者在接受伊匹单抗和纳武单抗联合治疗后无症状发生心肌炎的病例。
一名 71 岁亚裔男性，2 个月内出现发热、疲劳和体重减轻约 10kg，被诊断为 Xp.11.2 易位肾细胞癌。计算机断层扫描显示多个肺部肿块、纵隔淋巴结肿大和 II 级肿瘤栓子到达下腔静脉（cT3bN0M1；国际转移性肾细胞癌数据库联盟，高危）。作为诱导治疗开始使用伊匹单抗/纳武单抗联合治疗。治疗开始后，患者发生免疫相关不良反应急性间质性肾炎，但对皮质类固醇治疗反应良好。免疫治疗的抗肿瘤效果显著。尽管他发生了肺栓塞，但似乎无症状且无害，因此进行了第二次输注。从第 8 天开始，他出现了进行性恶化的心源性休克，伴有无症状的心电图变化和心脏生物标志物的急剧下降，并诊断为免疫相关的心肌炎。尽管立即给予甲基强的松龙小剂量脉冲治疗，然后逐渐减少泼尼松剂量，防止了死亡，但仍遗留广泛的心肌纤维化和明显的射血分数下降。因此，进行了无治疗的随访；然而，最初观察到的大部分肿瘤反应在几个月内仍得以维持。
治疗接受免疫检查点抑制剂治疗的患者的医生应意识到其潜在的危及生命的心脏毒性作用。本研究强调了在接受免疫治疗后出现心脏异常和可能的心肌炎的患者中，高度怀疑、及时诊断和早期干预的重要性。
