Checkpoint inhibitor-induced myocarditis and myasthenia gravis in a recurrent/metastatic thymic carcinoma patient: a case report

Abstract

Background Pembrolizumab, an immune checkpoint inhibitor (ICI), is an IgG4 antibody that blocks interaction between programmed cell death protein 1 and programmed death-ligand 1. Myocarditis, an immune-related adverse event, has been reported in thymic epithelial tumours. Pembrolizumab has also been associated with development/exacerbation of myasthenia gravis (MG). Case summary A 70-year-old woman with metastatic thymic cancer presented to the hospital with shortness of breath, 21 days after initiation of pembrolizumab. She was diagnosed with ICI-related myocarditis and was subsequently intubated due to respiratory failure. A dual-chamber pacemaker was placed due to complete heart block with asystole. Her troponin levels were elevated, an electrocardiogram was suspicious for myocardial infarction, but coronary angiogram revealed normal coronary arteries and endomyocardial biopsy confirmed the presence of myocarditis. Treatment was started with high-dose intravenous methylprednisolone and cardiovascular status improved. However, the patient was unable to be weaned from mechanical ventilation and tested positive for acetylcholine receptor binding/blocking antibodies due to de novo MG. After 50 days of hospitalization, she was discharged home in stable condition. A computed tomography scan was performed 6 weeks after pembrolizumab; results showed significant decrease/resolution of all measurable sites of metastatic disease in the lungs. Discussion This is the first reported case of a patient developing single-agent pembrolizumab-induced myocarditis concomitant with new-onset MG after treatment for advanced thymic malignancy. Additional studies are needed to explore the association between myocarditis, MG, and ICI therapy.

Immune Checkpoint Inhibitor–Induced Myocarditis with Myositis/Myasthenia Gravis Overlap Syndrome: A Systematic Review of Cases

“…(5) Twenty two patients were reported to have concomitant myasthenia gravis. (4,(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) The median number of doses to the development of IM3OS was one. The mean creatine kinase (CK) level was 9645 IU/L.…”

“…(13) Some cases also described early interstitial fibrosis and endocardial fibrosis in areas of inflammatory infiltration, likely representing healing response. (18,33,35)Two case reports specifically described negative staining for CD20 expressing B lymphocytes. (35,39)…”

Case Report: Lymphocytosis Associated With Fatal Hepatitis in a Thymoma Patient Treated With Anti-PD1: New Insight Into the Immune-Related Storm

“…In the scientific literature, case series of Pembrolizumab or Avelumab also in thymoma subjects have been reported ( 10 , 12 ). Despite an evident anti-tumor activity, immune-checkpoint inhibitors (ICIs) have displayed a critical immune-mediated toxicity profile; therefore, their safety represents an evolving landscape ( 10 , 12 , 13 ). Specifically, severe systemic ICI-related side effects in patients with thymoma have been described, including myocarditis, hepatitis, and myositis, highlighting the importance of careful patient selection while evaluating immunotherapeutic agents for treatment ( Supplementary Table 1 ) ( 10 , 12 , 14 , 15 ).…”

Checkpoint inhibitor-induced fulminant myocarditis, complete atrioventricular block and myasthenia gravis—a case report

“…Thymic epithelial tumors are more often associated with ICI-related myocarditis (9), as described in the nonrandomized phase II trial that evaluated pembrolizumab in platinum-based chemotherapy refractory patients, with high rates of grade ≥3 irAEs in patients with thymoma (71%), including myocarditis, myasthenia gravis and hepatitis (10). Concurrence of myocarditis and myasthenia gravis after immune therapy with pembrolizumab in a metastatic thymoma patient has already been described (11). Our patient received aggressive medical treatment with high-dose corticosteroids, infliximab and intravenous immunoglobulin because options for the management of advanced heart failure and myasthenia gravis were limited in the setting of active malignancy.…”