Table 2.
Case series.
| Subject number | Treatment (dose)54 | Indication | Treatment duration | Time to myocarditis onset after first drug exposure | Adverse events by grade | ||||
|---|---|---|---|---|---|---|---|---|---|
| Grade 1 AE | Grade 2 AE | Grade 3 AE | Grade 4 AE | Grade 5 AE (resulting in death) | |||||
| 1 | Carboplatin AUC of 6 mg.mL/min q3w + + pemetrexed 500 mg/m2 q3w | NCSLC | 81 days | 59 days |
Conjunctivitis Cough Dysgeusia Dysgeusia Dyspnea Herpes simplex Mucosal inflammation Nausea Pyrexia Rash Tachycardia |
Dyspepsia Fatigue Lethargy |
Myocarditis | None reported | None reported |
| 2 | Atezolizumab 1200 mg q3w + cisplatin 75 mg/m2 q3w + pemetrexed 500 mg/m2 q3w | NCSLC | 22 days | 42 days |
C-reactive protein increased Oxygen saturation decreased |
None reported |
Decreased appetite General physical health deterioration Myocarditis Transient ischemic attack |
Lung infection | None reported |
| 3 | Cemiplimab (3 mg/kg Q2W) | CSCC | 57 days | 58 days |
Alanine aminotransferase increased Aspartate aminotransferase increased Back pain Blood alkaline phosphatase increased Blood creatine phosphokinase increased Blood creatine phosphokinase MB increased Oral contusion Sensitivity to weather change |
Conjunctivitis Eye contusion Eye swelling Visual impairment |
Myocarditis | None reported | None reported |
| 4 | Durvalumab (10 mg/kg Q2W) | Listed as SCLC and solid tumors | 1 day | 4 days |
Abdominal pain [TR] Ascites [TR] (DW) Back pain Nausea [TR] Oedema peripheral [TR] Troponin increased [TR] Vomiting [TR] |
Ascites Dyspnea [TR] Fatigue [TR] Hyperglycemia Myocarditis |
Myocarditis Pancreatic carcinoma Troponin increased [TR] |
None reported | Pancreatic carcinoma |
| 5 | Ipilimumab (10 mg/kg q3w) | Melanoma | 22 days | 28 days |
Diarrhea [+++] Fatigue Musculoskeletal pain Pain in extremity |
Cholecystitis Groin pain Hemoglobin decreased Injection-site reaction Periarthritis Pyrexia Allergic rhinitis [+ +] |
Hepatitis [+++] (DW) Myocarditis [+++] (DW) Pneumonitis [+++] (DW) |
None reported | None reported |
| 6 | Ipilimumab (1 mg/kg) | Melanoma | 578 days | 27 days |
Sinus bradycardia [+] (DR) Ventricular extrasystoles [+] (DR) |
Blood creatinine increase (DR) Confusional state (DR) |
Supraventricular arrhythmia Aspartate aminotransferase increased Blood bilirubin increased Colitis [++] Diarrhea [+] (DW) Hypophosphatemia Hypotension (DR) Leukopenia Lymphopenia Myocarditis |
None reported | None reported |
| 7 | Ipilimumab (1 mg/kg) + nivolumab (3 mg/kg) | Bladder cancer | 64 days | 89 days |
Acute kidney injury Alanine aminotransferase increased [TR] Anemia [TR] Aspartate aminotransferase increased [TR] Blood albumin decreased Blood alkaline phosphatase increased Blood calcium decreased Blood creatine increased Blood phosphorus decreased Blood urea increased Depression Dry mouth [TR] Dry skin [TR] Hyperthyroidism [TR] Hypomagnesaemia Hypomagnesaemia Edema peripheral Oral candidiasis [TR] Pelvic pain Troponin I increased [TR] Tumor hemorrhage Weight decreased |
Angina pectoris [TR] Blood bicarbonate increased [TR] Blood creatine phosphokinase increased [TR] Blood creatine phosphokinase MB increased [TR] Blood gases abnormal [TR] Blood lactic acid decreased Blood lactic acid decreased Blood potassium increased Carbon dioxide increased [TR] Dysgeusia [TR] Escherichia infection Lymphocyte count decreased Malaise [TR] Nausea Neutrophil count increased [TR] Pelvic pain Urinary tract infection Weight decreased |
Angina pectoris [TR] Blood creatine phosphokinase increased [TR] Blood creatine phosphokinase MB increased [TR] Constipation [TR] Dry mouth [TR] Dyspnea Myocarditis [TR] Nausea Oral candidiasis [TR] Pelvic pain Stridor [TR] Troponin I increased [TR] Vomiting [TR] (DD) |
Myocarditis [TR] | Malignant neoplasm progression |
| 8 | Pembrolizumab (2 mg/kg Q3W) | MCC | 1 day | 26 days |
Anemia [TR] Asthenia [TR] Bundle branch block left [TR] Burning sensation [TR] Delirium [TR] Disorientation [TR] Dizziness [TR] Eyelid ptosis [TR] Fall [TR] Leukocytosis [TR] Ophthalmoplegia [TR] Oral candidiasis [TR] Proteinuria [TR] |
Acute kidney injury [TR] Atrial fibrillation [TR] Fatigue [TR] Hypertension [TR] Malnutrition [TR] |
Acute myocardial infarction [TR] Alanine aminotransferase increased [TR] Aspartate aminotransferase increased [TR] Blood creatine phosphokinase increased [TR] Cardiac failure acute [TR] Encephalopathy [TR] Hyponatremia [TR] Ventricular arrhythmia [TR] Ventricular tachycardia [TR] |
Hyperglycemia [TR] Myocarditis [TR] Small intestinal hemorrhage [TR] |
None reported |
| 9 | Pembrolizumab (200 mg Q3W) | NSCLC | 540 days | 557 days |
Abdominal pain upper[TR] Alanine aminotransferase increased [TR] Aspartate aminotransferase increased [TR] Blood alkaline phosphatase increased [TR] Cardiac failure [TR] Cough Decreased appetite Dyspnea Eczema [TR] Pruritus [TR] |
Cough Diarrhea Papule |
Acidosis Myocarditis [TR] |
None reported | None reported |
| 10 | Pembrolizumab (200 mg Q3W) | Bladder cancer | 129 days | 141 days |
Atrioventricular block first degree Blood alkaline phosphatase increased Blood bilirubin increased Bone pain Decreased appetite Fatigue Lymphadenopathy Pleural effusion Pruritus |
None reported |
Hepatic enzyme increased [TR] Myocarditis [TR] Scrotal oedema |
None reported | None reported |
| 11 | Pembrolizumab (200 mg Q3W) | Bladder cancer | 23 days | 34 days | Blood thyroid stimulating hormone increased [TR] | None reported |
Back pain [TR] Eyelid ptosis [TR] Fatigue [TR] Hepatitis [TR] Pneumonia [TR] Thyroiditis [TR] |
Myocarditis [TR] | Myositis [TR] |
| 12 | Pembrolizumab (200 mg Q3W) | Melanoma | 127 days | 138 days | Weight decreased [TR] | Iodine deficiency |
Myocarditis [TR] Myocarditis [TR] |
None reported | None reported |
| 13 | Pembrolizumab (200 mg Q3W) | HL | 1 day | 15 days |
Diarrhea [TR] Headache [TR] |
Tachycardia [TR] Thrombocytopenia Transaminases increased [TR] |
Bacteremia Dyspnea [TR] Myositis [TR] Weight decreased [TR] |
Myocarditis [TR] | None reported |
| 14 | Pembrolizumab (200 mg Q3W) + Axitinib (5 m BID) | RCC | 17 days | 17 days | Dysphonia [TR] |
Chest pain Fatigue [TR] Musculoskeletal chest pain |
None reported | None reported | Myocarditis [TR] |
| 15 | Pembrolizumab (200 mg Q3W) + Axitinib (5 m BID) | RCC | 43 days | 46 days |
Clostridium difficile colitis Erythema Insomnia Pneumonia |
Diarrhea [TR] |
Decreased appetite [TR] Electrolyte imbalance [TR] |
Hepatic function abnormal Myocarditis [TR] |
None reported |
| 16 | Avelumab (20 mg/kg Q2W) | Thymoma | 15 days | 18 days |
Dizziness Pyrexia Weight increased |
None reported |
Autoimmune disorder [TR] (DW) Blood creatine phosphokinase increased [TR] (DW) |
None reported | None reported |
| 17 | Avelumab (10 mg/kg Q2W) | Head and neck cancer | 197 days | 207 days |
Fatigue Myocarditis Pleural effusion |
Hypothyroidism Myocarditis Pleural effusion |
None reported | None reported | None reported |
[+++] = Certain AERELL; [++] = Probable AERELL; [+] = Possible AERELL; [TR] = Treatment related, plausibility unspecified.
DR dose reduced, DW drug withdrawn, DD dose delayed. Cases are part of the approval packages for the listed ICIs (see PharmaPendium).