Pembrolizumab/sintilimab

Abstract

Myocarditis: 2 case reports In a case series, two female patients aged 46-68 years were described, who developed drug-related myocarditis during treatment with sintilimab or pembrolizumab for beast cancer or metastatic malignancy of supraclavicular lymph node, respectively. This report describes a 68-year-old woman, who developed drug-related myocarditis during treatment with sintilimab: The woman with stage 4 breast cancer and Hodgkin’s lymphoma. She presented with fatigue and dyspnoea 3 weeks after she had received one dose of IV sintilimab 200mg every three weeks. Thus, treatment with sintilimab was stopped, and she admitted to hospital immediately. Upon admission, laboratory examinations showed increased levels of creatinine kinase (CK), creatine kinase isoenzyme-MB (CKMB) and cardiac troponin T (cTnT). Moreover, N-terminal pro-brain natriuretic peptide (NT-proBNP) was elevated at 507 pg/mL initially and later peaked at 2023 pg/mL. Antinuclear antibody (ANA) was positive with a titer of 1: 1000. Additionally, her inflammatory cytokines levels such as tumor necrosis factor (TNF), interleukin-2 receptor (IL-2R) and IL-6 were markedly elevated. Subsequent ECG revealed sinus tachycardia, frequent atrial premature beats and ST-T changes. Cardiac MRI (CMRI) revealed suspected left ventricular myocardial oedema with delayed enhancement, which was consistent with the changes in myocarditis. Based on these examinations and her symptoms, diagnosis of sintilimab-related myocarditis was made. Hence, she started receiving treatment with methylprednisolone; however, no significant improvement was noted. Later, she was transferred to the ICU, where she was administered with plasma exchange twice on day 4 and day 7 after admission. However, her symptoms persisted. Considering the poor response of treatment, treatment with tofacitinib was initiated. At the same time, she was initiated on nutritional myocardium, unspecified diuretic, unspecified beta-blocker and unspecified ACE inhibitor. Two days after tofacitinib treatment, she experienced rapid clinical improvement in her condition. On day 30 after diagnosis of myocarditis, significant decrease in myocardial markers was noted. Thereafter, she was discharged from hospital with methylprednisolone switched to prednisone and continued on tofacitinib. Her treatment with sintilimab was permanently discontinued. One month after discharge, she was doing well, with no cardiac symptoms and no tumour recurrence, and tofacitinib was stopped after 40 days of discharge. This report describes a 46-year-old woman, who developed drug-related myocarditis during treatment with pembrolizumab: The woman with metastatic malignancy of supraclavicular lymph node started receiving treatment with pembrolizumab [dosage and route not stated]. After 5 doses of pembrolizumab treatment, she started complaining of palpitations and dyspnoea without any known cardiac history. She admitted to hospital. Upon admission, her initial CK level was 196 U/L, CKMB was 9.6 ng/mL and cTnT was elevated at 0.113 ng/mL. Autoantibody test revealed ANA positive with a titer of 1: 1000. Subsequently, laboratory examinations showed elevated levels of multiple cytokines such as TNF, IL-2R and IL-6 in peripheral blood. Later, CMRI showed left ventricular myocardial oedema with little delayed enhancement, which was consistent with the changes in myocarditis. Based on these findings and her symptoms, diagnosis of pembrolizumab-related myocarditis was made. Thus, treatment with methylprednisolone was started on day 1 of admission; however, no significant improvement was noted. She continued to have dyspnoea and palpitations. Thus, she was administered with immune globulin on day 3 for three days. However, her symptoms did not improve significantly and cTnT continued to increase within 6 days of initiating methylprednisolone and immune globulin. Due to its refractory myocarditis, treatment with tofacitinib was subsequently initiated to treat the refractory myocarditis. One week after tofacitinib therapy, all her symptoms were markedly ameliorated, methylprednisolone was switched to prednisolone and she was discharged from hospital. She continued to receive tofacitinib for 2 months. At the time of report, the remission was sustained without apparent adverse events.