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Tab. 1 Patients’ characteristics, overview of cardiologic side effects and outcome

From: Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy

Pat-ID Age (y) Gender (m/f) Type of pathology (cardiomyopathy, heart block, etc.) Occured in week xxx after initiation of checkpoint inhibitor therapy Signs and symptoms Treatment of side effect Outcome of side effect (resolved/permanent changes/other) Other immune-related AEs Ipilimumab (number of doses and dosage) Nivolumab or Pembrolizumab (number of doses and dosage) Clinical response (CR, PR, MR, SD, PD) Survival in months from time of distant metastases
1 72 M myocarditis and cardiomyopathy week 22 Clinical findings: edema, ascites, pleural effusion, dyspnea diuresis, steroids (1 mg/kg), life vest good regression of symptoms under steroid therapy; slight permanent decrease in EF thyroiditis, hypophysitis Ipilimumab 3 mg/kg x 4 Nivolumab 1 mg/kg x 4 followed by 3 mg/kg x 6 PR 22
ECHO: EF from 50 % down to 15 % und up again to 40 %; dilatation of heart
Stress MRI: DCM, EF 15-23 %, no signs for ischemia
Cardiac catheterization: no signs for ischemia
Endomyocardial biopsy: interstitial inflammation mainly with lymphocytes and interstitial fibrosis
2 68 M cardiomyophathy week 12 Clinical findings: dyspnea, edema diuresis resolved none Ipilimumab 3 mg/kg x 4 no PD 40+
Echo: decrease of EF to 46 %; mild LV dysfunction; increased pulmonary pressures with moderate tricuspid regurgitation
Endomyocardial biopsy: Myocyte hypertrophy, interstitial and perivascular fibrosis, mild focal subendocardial myocyte vacuolization. Focal fibrous endocardial thickening.
Transmission electron microscopy: mild perinuclear accumulation of lysosomes, consistent with lipofuscin pigment deposition; increase of cytoplasmic glycogen and the number of mitochondria, without anomalous forms.
Cardiac catheterization: no evidence of coronary artery disease, however, measurements of his right heart pressures suggested an RA pressure of 16, RV pressure of 67/10, wedge of 23 and PA pressures of 68/39
3 61 M myocardial fibrosis week 4 Clinical findings: no cardiologic symptoms steroids (2 mg/kg), intensive care unit fatal; massive autoimmune side effects could not be overcome autoimmune hepatitis Ipilimumab 3 mg/kg x 2 no died of side effects 3
Endomyocardial biopsy: myocardial fibrosis identified at autopsy
4 81 M heart failure week 22 Clinical findings: dyspnea diuresis permanent decrease in EF colitis, hypophysitis Ipilimumab 3 mg/kg x 3 no PR 22+
ECHO: moderately-to-severely reduced left ventricular EF at 35 %; mildly dilated left ventricle; global hypokinesis with regional variation; akinetic basal inferior and inferoseptal segments
5 23 M myocarditis/CHF week 31 Clinical findings: cardiogenic shock requiring dopamine and dobutamine gtt High dose steroids 2 mg/kg methylprednisolone per day converted to 80 mg prednisone/d with taper over 1 month, ACEi and beta blocker resolved to baseline (NYHA C1) uveitis Ipilimumab 3 mg/kg x 4 no SD 31
Endomyocardial biopsy: T cell infiltration without eosinophilia
ECHO: drop of EF to 20 %
Cardiac MRI: left ventricular dilation and moderate LV systolic dysfunction (LVEF 34 %); right ventricular dilation and moderate RV systolic dysfunction (RVEF 33 %); increased T2 signal in the mid-inferolateral wall, suggestive of underlying myocardial edema supportive of myocarditis.
6 64 M myocarditis week 5 Clinical findings: fatigue, seizures, abdominal pain dopamine and fentanyl fatal none Ipilimumab 10 mg/kg x 2 no NA died of side effects
Cardiac catheterization and electrocardiogram: normal
evidence of myocarditis and LV hypertrophy upon autopsy
7 88 M cardiac arrest week 20 Clinical findings: collapse with cardiac arrest during shopping without any prodromi AED with defibrillation, intensice care unit, catecholamines, steroids (125 mg i.v./d) resolved none no Pembrolizumab 2 mg/kg x 9 PR 8+
ECHO: akinesis of the apex
Cardiac catheterization and electrocardiogram: coronary artery disease with no culprit stenosis, reduced LV function; similar to taktsubo cardiomyopathy
8 80 M myocarditis week 5 Clinical findings: dyspnea, edema, arrhythmias steroids (10 mg dexamethasone + 4 mg every 4 h), intensive care unit fatal autoimmune hepatitis Ipilimumab 3 mg/kg x 2 no PR died of side effects
EKG: atrial fibrillation, right bundle-branch block
Nuclear stress test: no stress-induced ischemia
ECHO: drop of EF to 31 %, hypokinesis
Endomyocardial biopsy: Multinucleated giant cells, lymphocytes, eosinophils