Table 3.

Clinical cases of PEM-induced irAEs

Clinical Case, Year Reported	Age/Sex (M/F)	PEM Oncological Indication	Reported PEM-Induced CVD Clinical Indications	PEM-Induced irAEs Clinical Presentation
Case 1, 2021 (145)	75	Malignant mesothelioma	Elevated CK, CK-MB, troponin-T ST segment elevation Severely reduced EF%	Myocarditis Hemodynamic compromise
Case 2, 2021 (60)	49/F	Thymoma	Elevated CK, troponin-T	Dysarthria Dysphagia Dyspnea Limb weakness Myocarditis
	70/M	Bladder cancer	Elevated CK, troponin-T	Ptosis Dyspnea Diplopia Muscle pain
	75/M	Chondroma of SACRUM	Elevated CK, troponin-T	Ptosis Diplopia Lower extremity edema
Case 3, 2021 (146)	83/M	Advanced nonsmall cell lung cancer	Elevated CK-MB, troponin-I, C-reactive protein ST-segment depression	Chest pain Dyspnea
Case 4, 2020 (147)	79/M	Metastatic melanoma	Elevated CK, troponin	Fatigue Lower extremity weakness Complete heart block Pulmonary embolism
	69/M	Metastatic urothelial carcinoma	Elevated troponin EF% of 40%–45%.	Diffuse body pain and weakness Concentric hypertrophy NSTEMI Stroke Hemiparesis
	89/M	Nonsmall cell lung cancer	Elevated CK, troponin EF% of 47%	Ventricular tachycardia Atrioventricular block Myositis Persistent weakness Dysphagia, blurred vision
Case 5, 2020 (148)	75/M	Lung adenocarcinoma	Elevated CK, CK-MB, troponin-I Extensive infiltration of CD8+ T cells and histiocyte infiltrates	Myalgia Palpitations Myocarditis Complete atrioventricular block Necrotizing myocarditis Necrotizing myopathy
Case 6, 2020 (149)	69/M	Urothelial carcinoma	Elevated CK, myoglobin, troponin-T Wide QRS complex ventricular rhythm Myocardial and muscle biopsy showed immune infiltration and inflammation in myofibers	Myalgia Severe fatigue and abnormal gait Reduced muscle reflexes and proximal muscle weakness Myositis proceeding to myocarditis
Case 7, 2020 (150)	77/M	Metastatic melanoma	Elevated CK, troponin, and creatine T-wave inversion	Acute weakness and fatigue Necrotic myopathy Myositis
Case 8, 2020 (151)	63/M	Bladder tumor	Elevated CK, CK-MB, troponin-I	Myositis Ptosis Diplopia Systemic myopathy
Case 9, 2020 (152)	70/F	Thymic carcinoma	Elevated CK, CK-MB, troponin-T T-wave inversions ST elevation Complete heart block Infiltrating lymphocytes and macrophages Early interstitial fibrosis and endocardial fibrosis in areas of immune infiltration	Dyspnea, orthopnea, and weakness Myocarditis Complete atrioventricular heart block Left lower lobe pulmonary embolism Anterior myocardial infarction
Case 10, 2019 (153)	83/M	Urothelial carcinoma	Elevated CK, CK-MB, troponin-I EKG showed T-wave abnormalities and nonspecific intraventricular conduction block	Fatal myocarditis Complete heart block Toxic myopathy/myositis
Case 11, 2019 (154)	70/M	Squamous cell carcinoma of the right lung	Elevated CK, CK-MB, troponin-T LVEF of 29% Lymphocytic infiltration in myocardial biopsy	Fulminant myocarditis Refractory ventricular fibrillation and circulatory failure
Case 12, 2019 (155)	58/F	Metastatic thymoma	Elevated troponin LVEF < 30% Diffuse hypokinesia of the heart	Anterior myocardial infarction Acute heart failure Decompensated heart failure Ventricular arrhythmia
	30/F	Metastatic B3 thymoma	Elevated CK, troponin-I	Acute chest pain Proximal muscle weakness Myositis/myocarditis
Case 13, 2019 (156)	83/M	Metastatic melanoma	Elevated CK, CK-MB, troponin-T, BNP T-wave abnormality, wide QRS, atrioventricular block	Fatigue and muscle pain Bilateral ptosis Diplopia Weakness of neck flexor and extensor Bilateral thigh myalgia Dysphagia and dyspnea Myositis and myocarditis
Case 14, 2018 (157)	67/F	Multiple myeloma	Elevated CK, CK-MB, troponin-T ST-segment elevation Complete AV block LVEF below 30% Infiltration of cytotoxic T cells and macrophages Collagen fibrosis in the myocardium	Myositis Myocarditis Depressed ventricular contractility without focal hypokinesis Ventricular tachycardia
Case 15, 2018 (158)	79/M	Metastatic gastric adenocarcinoma	Elevated CK, CK-MB, troponin-I Necrotic myofibers and infiltration of T cells and macrophages	Bilateral asymmetric ptosis Bilateral ptosis Myositis and myocarditis Dysphagia and bradycardia Atrioventricular block
Case 16, 2017 (159)	78/M	Metastatic melanoma	Elevated CK Reduced muscle action potential amplitudes Necrotic muscle fibers with immune infiltration	Acute onset of bulbar weakness Dysarthria Bilateral asymmetric ptosis Bifacial paresis Ophthalmoparesis Bilateral proximal limb muscle weakness Dysphagia Myalgia Muscle weakness in extremities Necrotizing myopathy Myositis of the diaphragm Myocarditis
Case 17, 2017 (160)	82/M	Melanoma	Elevated LDH, CK, C-reactive protein	Ptosis and miosis Proximal muscle weakness of the lower limbs Neck and shoulder pain unresponsive to painkillers and muscle relaxants Dysphagia, stridor, hypokinesis
Case 18, 2016 (161)	86/F	Metastatic melanoma	Elevated CK Muscle biopsy revealed necrosis with T-cell infiltration	Fatigue Left ptosis Ophthalmoplegia Proximal bilateral limb weakness Dyspnea Necrotizing myositis

BNP, brain natriuretic peptide; CK, creatine kinase; CK‐MB, creatine kinase myocardial band; CVD, cardiovascular disease; EF, ejection fraction; EKG, echocardiogram; irAEs, immune‐related adverse events; LDH, lactose dehydrogenase; LVEF, left ventricular ejection fraction; NSTEMI, non‐ST‐elevation myocardial infarction; PEM, pembrolizumab.