Lee Dae Hyun, Armanious Merna, Huang Jessica, Jeong Daniel, Druta Mihaela, Fradley Michael G
Department of Cardiovascular Sciences, University of South Florida, Morsani College of Medicine and Cardio-Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
J Oncol Pharm Pract. 2020 Sep;26(6):1544-1548. doi: 10.1177/1078155220904152. Epub 2020 Feb 23.
Pembrolizumab is an immune checkpoint inhibitor targeting the programmed death receptor with clinical effect on multiple malignancies including sarcoma. Associated cardio-toxicities include myocarditis, cardiomyopathy, heart failure, and arrhythmias. Although in most cases of immune checkpoint inhibitor cardiotoxicity the offending agent is discontinued, we report a case of successful and safe re-challenge with a checkpoint inhibitor in a patient with mild myocarditis.
We describe a 37-year-old female with alveolar soft part sarcoma, metastatic to the lungs on cycle 13 of pembrolizumab who presented with dyspnea, cough, and vague chest discomfort. Telemetry showed bigeminal bradycardia that transitioned to self-terminating torsades de pointes. Cardiac MRI showed subtle patchy T2 signal increase within the left ventricular septum without late gadolinium uptake, suggesting mild focal myocarditis.Management and outcome: The patient was started on a steroid taper without additional arrhythmias. We have re-challenged the patient who safely tolerated re-challenge with pembrolizumab despite an episode of torsades de pointes and documented myocarditis. She continues to receive pembrolizumab at seven months after the initial event without further cardiovascular events.
To the best of our knowledge, this is the first reported case of successful re-challenge of pembrolizumab after an episode of myocarditis. In patients with mild myocarditis and no evidence of left ventricular dysfunction, re-challenge may be a viable option. However, close monitoring for the development of heart failure, cardiomyopathy, or serious arrhythmias is necessary to ensure patient safety.
帕博利珠单抗是一种靶向程序性死亡受体的免疫检查点抑制剂，对包括肉瘤在内的多种恶性肿瘤具有临床疗效。相关的心脏毒性包括心肌炎、心肌病、心力衰竭和心律失常。尽管在大多数免疫检查点抑制剂心脏毒性病例中会停用致病药物，但我们报告了一例在轻度心肌炎患者中成功且安全地重新使用检查点抑制剂的病例。
我们描述了一名37岁患有肺泡软组织肉瘤的女性患者，在接受帕博利珠单抗治疗的第13个周期出现肺部转移，表现为呼吸困难、咳嗽和模糊的胸部不适。遥测显示成对的心动过缓，随后转变为自行终止的尖端扭转型室速。心脏磁共振成像显示左心室间隔内T2信号轻微片状增加，无延迟钆摄取，提示轻度局灶性心肌炎。
患者开始逐渐减量使用类固醇，未再出现其他心律失常。尽管发生了一次尖端扭转型室速并记录有心肌炎，但该患者安全耐受了帕博利珠单抗的重新给药。在初次事件发生七个月后，她继续接受帕博利珠单抗治疗，未再发生心血管事件。
据我们所知，这是首例报告的心肌炎发作后成功重新使用帕博利珠单抗的病例。对于轻度心肌炎且无左心室功能障碍证据 的患者，重新给药可能是一种可行的选择。然而，为确保患者安全，有必要密切监测心力衰竭、心肌病或严重心律失常的发生情况。
