Nivolumab-induced Myocarditis Successfully Treated with Corticosteroid Therapy: A Case Report and Review of the Literature

Matsuo, Keisuke; Ishiguro, Takashi; Najama, Takatomo; Shimizu, Yoshihiko; Kobayashi, Yasuhito; Mutou, Makoto

As an ICI, nivolumab is a novel remedy for malignant tumors that promotes the attack of cancer cells by lymphocytes by suppressing the expression of PD-1 on the cell surface of cancer cells. Nivolumab has transformed the treatment of several cancers by releasing restrained antitumor immune responses (14) . Treatment with nivolumab is known to cause several ir-AEs, including thyroid dysfunction, colitis, pneumonitis, and rarely, type 1 diabetes, Guillain-Barré syndrome, and myasthenia gravis. However, the frequency of myocarditis is 0.06% (8), whereas the frequencies of myocarditis due to other ICIs, such as pembrolizumab and atezolizumab, in Japan are reported to be 3 in 4,259 patients (0.07%) (15) and 2 in 2,800 patients (0.07%) (16), respectively. Although its probability of occurrence is not high, myocarditis is an ir-AE that cannot be ignored due to the possibility of a fatal outcome. To our knowledge, only 13 cases of myocarditis induced by nivolumab have been reported (Table) . Among these 13 cases, the patients' ages ranged from 49 to 80 years, and 9 men were included. Malignancies for which nivolumab was administered included melanoma in eight cases, lung cancer in four cases, and glioblastoma in one case. Development of nivolumabinduced myocarditis occurred after the initial administration of nivolumab in five cases, after the second administration in three cases, after the third administration in three cases, after the ninth administration in one case, and after the tenth administration in one case. Our patient developed myocarditis one year after the initiation of nivolumab but during the third readministration after a two-month period of drug cessation due to hypothyroidism. As our case indicates, nivolumab-induced myocarditis can develop even one year after its administration. Thus, clinicians should consider nivolumab as a cause of myocarditis even if one year has passed from its introduction.