Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website https://www.cardiologyres.org

Review

Volume 12, Number 5, October 2021, pages 270-278

Clinical Characteristics and Outcomes in Immune Checkpoint Inhibitor Therapy-Associated Myocarditis

**Table 1.** Patient Characteristics
	N	%
Gender
Male	46	64.8%
Female	24	33.8%
No gender provided	1	1.4%
Pretreatment cardiovascular diagnosis
Atrial fibrillation/atrial flutter	1	4.8%
History of arrhythmia	2	9.5%
History of coronary artery bypass grafting	2	9.5%
History of valve repair	1	4.8%
Hyperlipidemia	6	28.6%
Hypertension	19	90.5%
Myocardial infarction	1	4.8%
Peripheral artery disease	2	9.5%
Not provided/not applicable	50
Malignancy
> 1 malignancy	2	2.8%
Clear cell renal cell carcinoma (ccRCC)	2	2.8%
Chronic myelomonocytic leukemia (CMML)	1	1.4%
Glioblastoma	1	1.4%
Head and neck squamous cell carcinoma	3	4.2%
Hepatocellular carcinoma (HCC)	1	1.4%
Large cell neuroendocrine carcinoma (LCNEC)	1	1.4%
Lymphoma	1	1.4%
Melanoma	24	33.8%
Mesothelioma	3	4.2%
Non-small cell lung carcinoma (NSCLC)	18	25.4%
Periocular squamous cell carcinoma	1	1.4%
Prostate adenocarcinoma	2	2.8%
Renal cell carcinoma (RCC)	5	7.0%
Sarcoma-alveolar soft part	1	1.4%
Serous endometrial carcinoma	1	1.4%
Thymic cancer	1	1.4%
Thymoma	1	1.4%
Urothelial cancer	2	2.8%

Table 1. Patient Characteristics

Gender

Male

64.8%

Female

33.8%

No gender provided

1.4%

Pretreatment cardiovascular diagnosis

Atrial fibrillation/atrial flutter

4.8%

History of arrhythmia

9.5%

History of coronary artery bypass grafting

9.5%

History of valve repair

4.8%

Hyperlipidemia

28.6%

Hypertension

90.5%

Myocardial infarction

4.8%

Peripheral artery disease

9.5%

Not provided/not applicable

Malignancy

> 1 malignancy

2.8%

Clear cell renal cell carcinoma (ccRCC)

2.8%

Chronic myelomonocytic leukemia (CMML)

1.4%

Glioblastoma

1.4%

Head and neck squamous cell carcinoma

4.2%

Hepatocellular carcinoma (HCC)

1.4%

Large cell neuroendocrine carcinoma (LCNEC)

1.4%

Lymphoma

1.4%

Melanoma

33.8%

Mesothelioma

4.2%

Non-small cell lung carcinoma (NSCLC)

25.4%

Periocular squamous cell carcinoma

1.4%

Prostate adenocarcinoma

2.8%

Renal cell carcinoma (RCC)

7.0%

Sarcoma-alveolar soft part

1.4%

Serous endometrial carcinoma

1.4%

Thymic cancer

1.4%

Thymoma

1.4%

Urothelial cancer

2.8%

**Table 2.** Patient Outcomes
	N	%
ICI therapy
Atezolizumab	1	1.4%
Cemiplimab	1	1.4%
Durvalumab	1	1.4%
Ipilimumab	1	1.4%
Multiple immune checkpoint inhibitors used	20	28.2%
Nivolumab	27	38.0%
Pembrolizumab	19	26.8%
Sintilimab	1	1.4%
Adverse events with coprevalent myocarditis
Acute kidney injury	6	9.2%
Acute liver injury	12	18.5%
Acute respiratory failure	5	7.7%
Adrenal insufficiency	1	1.5%
Arrhythmias	12	18.5%
Atrial fibrillation	5	7.7%
Autoimmune diabetes mellitus	1	1.5%
Colitis	3	4.6%
Encephalitis	1	1.5%
Heart block	18	27.7%
Heart failure	25	38.5%
Hypophysitis	1	1.5%
Myasthenia gravis/crisis	14	21.5%
Myositis	16	24.6%
Pericardial effusion	1	1.5%
Pneumonitis	5	7.7%
Rhabdomyositis	1	1.5%
Thyroiditis	2	3.1%
Not reported	6
Treatment
Corticosteroid therapy alone	40	56.3%
Intravenous immunoglobulin (IVIG) alone	1	1.4%
Anti-thymocyte globulin (ATG) alone	0	0.0%
Supportive care	1	1.4%
Corticosteroid + immunosuppressant (tacrolimus, mycophenolate mofetil)	3	4.2%
Corticosteroid + IVIG	6	8.5%
Corticosteroid + IVIG + immunosuppressant	1	1.4%
Not stated/no treatment	2	2.8%
Corticosteroid + ATG	2	2.8%
Corticosteroid + tofacitinib	1	1.4%
Corticosteroid + IVIG + tofacitinib	1	1.4%
Corticosteroid + infliximab	3	4.2%
Corticosteroid + IVIG + infliximab	1	1.4%
Corticosteroid + immunosuppressant + ATG + infliximab	1	1.4%
Any combination including plasma exchange/plasmapheresis	8	11.3%
Mortality
Alive	35	49.3%
Death	35	49.3%
Unknown	1

Table 2. Patient Outcomes

ICI therapy

Atezolizumab

1.4%

Cemiplimab

1.4%

Durvalumab

1.4%

Ipilimumab

1.4%

Multiple immune checkpoint inhibitors used

28.2%

Nivolumab

38.0%

Pembrolizumab

26.8%

Sintilimab

1.4%

Adverse events with coprevalent myocarditis

Acute kidney injury

9.2%

Acute liver injury

18.5%

Acute respiratory failure

7.7%

Adrenal insufficiency

1.5%

Arrhythmias

18.5%

Atrial fibrillation

7.7%

Autoimmune diabetes mellitus

1.5%

Colitis

4.6%

Encephalitis

1.5%

Heart block

27.7%

Heart failure

38.5%

Hypophysitis

1.5%

Myasthenia gravis/crisis

21.5%

Myositis

24.6%

Pericardial effusion

1.5%

Pneumonitis

7.7%

Rhabdomyositis

1.5%

Thyroiditis

3.1%

Not reported

Treatment

Corticosteroid therapy alone

56.3%

Intravenous immunoglobulin (IVIG) alone

1.4%

Anti-thymocyte globulin (ATG) alone

0.0%

Supportive care

1.4%

Corticosteroid + immunosuppressant (tacrolimus, mycophenolate mofetil)

4.2%

Corticosteroid + IVIG

8.5%

Corticosteroid + IVIG + immunosuppressant

1.4%

Not stated/no treatment

2.8%

Corticosteroid + ATG

2.8%

Corticosteroid + tofacitinib

1.4%

Corticosteroid + IVIG + tofacitinib

1.4%

Corticosteroid + infliximab

4.2%

Corticosteroid + IVIG + infliximab

1.4%

Corticosteroid + immunosuppressant + ATG + infliximab

1.4%

Any combination including plasma exchange/plasmapheresis

11.3%

Mortality

Alive

49.3%

Death

49.3%

Unknown

**Table 3.** Associated Mortality
	Mortality number	Mortality (%)
Gender
Male	24/46	52.2%
Female	9/24	37.5%
ICI therapy
Atezolizumab	1/1	100%
Cemiplimab	1/1	100%
Durvalumab	0/1	0%
Ipilimumab	0/1	0%
Nivolumab	14/27	51.9%
Pembrolizumab	7/19	36.8%
Multiple immune checkpoint inhibitors	10/20	50%
Associated adverse events by highest incidence
Heart failure	11/25	44%
Heart block	12/18	66.7%
Myositis	11/16	68.8%
Myasthenia gravis/crisis	5/14	35.7%
Arrhythmias	6/12	50.0%
Acute liver injury	7/12	58.3%
Acute kidney injury	4/6	66.7%

Table 3. Associated Mortality

Mortality number

Mortality (%)

Gender

Male

24/46

52.2%

Female

9/24

37.5%

ICI therapy

Atezolizumab

1/1

100%

Cemiplimab

1/1

100%

Durvalumab

0/1

Ipilimumab

0/1

Nivolumab

14/27

51.9%

Pembrolizumab

7/19

36.8%

Multiple immune checkpoint inhibitors

10/20

50%

Associated adverse events by highest incidence

Heart failure

11/25

44%

Heart block

12/18

66.7%

Myositis

11/16

68.8%

Myasthenia gravis/crisis

5/14

35.7%

Arrhythmias

6/12

50.0%

Acute liver injury

7/12

58.3%

Acute kidney injury

4/6

66.7%