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

A 62-year-old man with an unresectable lung adenocarcinoma of clinical stage cT1bN2M0 of the Eighth Lung Cancer Stage Classification (13) diagnosed in August 2013 presented to Saitama Cardiovascular and Respiratory Center complaining of back pain, chest discomfort, general fatigue, and dyspnea in September 2018 and was admitted for a further evaluation. Because of mild fibrosis for which the possibility of interstitial lung diseases on CT could not be ruled out, he had been receiving chemotherapy without radiation therapy since the diagnosis of adenocarcinoma. Since September 2013, he had undergone chemotherapy with cisplatin plus pemetrexed followed by maintenance chemotherapy with pemetrexed and docetaxel. In May 2017, because the contralateral mediastinal lymph node was enlarged, recurrence was diagnosed, and nivolumab was started biweekly. The swollen lymph nodes decreased in size, and no abnormal shadows were noted, so he was considered to be in complete remission. In November 2017, decreased FT3 and FT4 values and an elevated thyroid-stimulating hormone value indicating hypothyroidism were found, but there were no clinical symptoms, and we followed him without treatment. In July 2018, he developed general fatigue, and we considered the symptoms due to hypothyroidism and stopped the nivolumab. By August 2018, his general fatigue had improved, and we restarted the nivolumab. However, in September 2018, 4 days after the 29th administration of nivolumab, he developed back pain, chest discomfort, general fatigue, and dyspnea. His vital signs were as follows: blood pressure of 92/62 mmHg, heart rate of 85 beats/min, and respiratory rate of 20/min. Chest auscultation revealed an irregular heartbeat without murmurs or rales. Pitting edema was found in his lower extremities. The electrocardiogram showed wide QRS waves (Fig. 1A) . A transthoracic cardiac ultrasound examination showed an attenuated left ventricular ejection fraction of 45% compared with that of 70% in February 2014 and a decrease in the left ventricular wall motion in the posterior, inferior, and lateral walls. Laboratory data showed white blood cells of 6,200/mm 3 , hemoglobin of 13.1 g/dL, platelets of 205,000/mm 3 , serum creatine kinase value of 970 IU/ L (normal 56 to 244), and increases in creatine kinasemyocardial band to 78 ng/mL (normal <5 ng/mL) and cardiac troponin T to 4.81 ng/mL (normal <0.1 ng/mL). The Creactive protein value was also increased to 2.06 mg/dL. Autoantibodies, including antinuclear antibodies, anti-Acl-70 antibodies, anti-ARS antibodies, anti-ds DNA antibodies, anti-RNP antibodies, anti-SS-A/Ro, and anti-SS-B/La antibodies, were all negative. BNP was increased to 466 pg/mL, and chest X-ray showed cardiac enlargement with rightsided pleural effusion (Fig. 1B) .