Authors' Affiliations: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Cancer Immunol Res. 2014 Jan;2(1):15-8. doi: 10.1158/2326-6066.CIR-13-0146. Epub 2013 Oct 7.
Treatment with fully human monoclonal antibodies against programmed death 1 (PD1) receptor has shown great promise for a number of advanced malignancies. Although inflammatory adverse events have been well described with anti-CTL antigen 4 (CTLA4) therapy, experience with the range of adverse effects of anti-PD1 remains comparatively limited. Here, we report on a patient with advanced mucosal melanoma who received four doses of MK-3475, a fully human monoclonal antibody against PD1, and experienced a durable near-complete response but developed severe hypothyroidism, rhabdomyolysis, and acute kidney injury. To our knowledge, this is the first case reported of a patient with advanced mucosal melanoma who responded to anti-PD1 therapy. With the promising antitumor effects of anti-PD1 in a wide array of tumors, we expect an increasing number of patients to be exposed to anti-PD1 therapies. Recognition of infrequent presentations of adverse events such as elevated creatine kinase levels and thyroid disorders in patients who receive anti-PD1 therapy is important.
治疗晚期恶性肿瘤的完全人源化单克隆抗体抗程序性死亡受体 1(PD1)显示出巨大的潜力。虽然抗细胞毒性 T 淋巴细胞相关抗原 4(CTLA4)治疗的炎症不良反应已得到很好的描述,但抗 PD1 治疗的一系列不良反应的经验相对有限。在这里,我们报告了一名晚期黏膜黑色素瘤患者,他接受了 4 剂 MK-3475(一种针对 PD1 的完全人源化单克隆抗体)治疗,经历了持久的近乎完全缓解,但出现严重甲状腺功能减退、横纹肌溶解和急性肾损伤。据我们所知,这是首例报道的晚期黏膜黑色素瘤患者对 PD1 治疗有反应的病例。随着抗 PD1 在多种肿瘤中的抗肿瘤作用的显著疗效,我们预计会有越来越多的患者接受抗 PD1 治疗。识别接受抗 PD1 治疗的患者中肌酸激酶水平升高和甲状腺疾病等罕见不良反应的表现非常重要。