Department of Internal Medicine, University of Connecticut, CT, USA.
Department of Hematology/Oncology, University of Connecticut, CT, USA.
J Oncol Pharm Pract. 2021 Jan;27(1):207-211. doi: 10.1177/1078155220921543. Epub 2020 May 9.
Immune agents including anti-programmed death receptor-1 and anti-cytotoxic T-lymphocyte antigen-4 have been associated with numerous immune-related complications. Pembrolizumab, a programmed death-1 inhibitor, has been associated with a number of immune-related adverse events such as pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes.
We present a rare case of an elderly male on pembrolizumab who suffered from four autoimmune toxicities including type 1 diabetes, pneumonitis, hypothyroidism, and polymyalgia rheumatica likely catalyzed by age-related immune activation. Immunotherapy was indefinitely stopped, and patient was started on steroids for the immune-related adverse events with complete resolution of polymyalgia rheumatica. Thyroid dysfunction resolved once he started thyroid replacement therapy. His diabetes is well controlled with insulin and is followed by endocrinology. He continues on prednisone for immune-mediated pneumonitis with a good response with regular monitoring via computed tomography scans and pulmonary consultation.
Few cases wherein multiple toxicities are seen within one patient are reported. Aging appears to be a risk factor for immune-related adverse events. Aging is associated with an increased incidence of autoimmunity as programmed death-1 ligand expression represents an important mechanism that tissues use to protect from self-reactive effector T cells. Programmed death-1 blockade breaks this protective mechanism and enhances autoimmune diseases. Therefore, close monitoring and extreme vigilance is warranted while using immune checkpoint inhibitors including pembrolizumab as multiple toxicities can occur within a short span of infusion, especially in elderly individuals. Prompt discontinuation and the use of a multidisciplinary team are prudent to prevent further morbidity and mortality.
免疫制剂，包括抗程序性死亡受体-1 和抗细胞毒性 T 淋巴细胞抗原-4，与许多免疫相关的并发症有关。程序性死亡-1 抑制剂 pembrolizumab 与多种免疫相关的不良反应相关，如肺炎、结肠炎、肝炎、垂体炎、甲状腺功能亢进、甲状腺功能减退、肾炎和 1 型糖尿病。
我们报告了一例罕见的老年男性病例，该患者在接受 pembrolizumab 治疗后出现了四种自身免疫毒性，包括 1 型糖尿病、肺炎、甲状腺功能减退和多发性肌痛性风湿症，这些毒性可能是由年龄相关的免疫激活引起的。免疫治疗被无限期停止，患者开始接受皮质类固醇治疗免疫相关的不良反应，多发性肌痛性风湿症完全缓解。甲状腺功能减退一旦开始甲状腺替代治疗就得到了缓解。他的糖尿病通过胰岛素得到了很好的控制，并由内分泌科随访。他继续接受泼尼松龙治疗免疫介导的肺炎，定期通过计算机断层扫描和肺部咨询进行监测，反应良好。
很少有病例报告在一个患者中出现多种毒性。年龄似乎是免疫相关不良反应的一个危险因素。随着程序性死亡配体表达成为组织用于保护自身反应性效应 T 细胞的重要机制，衰老与自身免疫的发生率增加有关。程序性死亡-1 阻断打破了这种保护机制，增强了自身免疫性疾病。因此，在使用免疫检查点抑制剂（包括 pembrolizumab）时，需要密切监测和高度警惕，因为多种毒性可能在短时间内输注，特别是在老年患者中。及时停药和多学科团队的使用是明智的，可以预防进一步的发病率和死亡率。
