Cardiac adverse events of immune checkpoint inhibitors in oncology patients: A systematic review and meta-analysis

Table 1 Summary of baseline characteristics of included studies, n (%)

Study	n	ICI	Cancer type	Males	Median age (range), yr	Median follow-up (range), mo	Race, Asian	Race, Black	Tobacco users
Antonia et al[8], 2016a	98	Nivolumab	Small cell carcinoma of the lung	61 (62)	63 (57-68)	10.07 (NR)	NR	3 (3)	95 (97)
Antonia et al[8], 2016b	61	Nivolumab plus ipilimumab	Small cell carcinoma of the lung	35 (57)	66 (58-71)	12.03 (9.10-15.67)	NR	1 (2)	57 (93)
Antonia et al[8], 2016c	54	Nivolumab plus ipilimumab	Small cell carcinoma of the lung	32 (59)	61 (56-65)	8.68 (8.27-9.6)	NR	0	48 (89)
Antonia et al[21], 2017	476	Durvalumab	Stage III non-small cell lung cancer	334 (70.2)	64 (NR)	14.5 (0.2-29.9)	120 (25.2)	12 (2.5)	433 (91)
Balar et al[22], 2017	370	Pembrolizumab plus cisplatin	Advanced, unresectable metastatic urothelial cancer	286 (77)	74 (34-94)	5 (30-8.6)	NR	NR	NR
Barlesi et al[23], 2018	393	Avelumab	Advanced non-small-cell lung cancer	269 (68)	64 (59-70)	18.9 (IQR 13.2-23)	102 (26)	5 (1)	324 (82)
Bott et al[24], 2018	21	Nivolumab	Resectable non–small cell lung cancer	10 (48)	67 (55-84)	1.1 (0.57-1.13)	NR	NR	18 (86)
Brohl et al[25], 2016	31	Ipilimumab plus peginterferon	Unresectable melanoma	18 (58.1)	65 (38-83)	35.8 (19.7-50.2)	NR	NR	NR
Cho et al[26], 2018	33	Pembrolizumab	Relapsed thymic epithelial tumor	21 (63.6)	57 (26-78)	14.9 (IQR 6.25-20.7)	NR	NR	NR
Choueiri et al[3], 2018	55	Avelumab plus axitinib	Advanced clear cell renal cell carcinoma	42 (76)	60 (55–68)	13 (9.35-14.02)	6 (11)	3 (6)	NR
Chung et al[27], 2019	11	p53MVA vaccine combined with pembrolizumab	Advanced breast, pancreatic, hepatocellular, or head and neck cancer	NR	NR	16.26 (15.42-17.27)	NR	NR	NR
Dudnik et al[28], 2018	260	Nivolumab	Non-small cell lung cancer	176 (68)	67 (41-99)	8.4 (2-16.8)	NR	NR	197 (76)
Eggermont et al[29], 2015	475	Ipilimumab	High-risk stage III melanoma	296 (62)	51 (20-84)	7.5 (7-11.4)	NR	NR	NR
Giaccone et al[30], 2018	40	Pembrolizumab	Thymic carcinoma	28 (70)	57 (25-80)	8.4 (2-16.8)	4 (10)	2 (5)	NR
Herbst et al[31], 2020	26	Ramucirumab plus pembrolizumab	Advanced non-small-cell lung cancer	21 (78)	65 (56-72)	33.3 (IQR 27.7-39.2)	NR	1 (4)	26 (96)
Hodi et al[32], 2018	313	Nivolumab plus ipilimumab	Advanced melanoma	NR	NR	20 (IQR 14-26)	NR	NR	NR
Juergens et al[7], 2020	136	Durvalumab with or without tremelimumab and platinum-doublet	Lung cancer (unspecified)	67 (49)	61.9 (30.1-83.2)	32.8 (IQR 28.1-33.6)	8 (6)	1 (1)	NR
Loi et al[33], 2019	58	Pembrolizumab plus trastuzumab	Lung cancer (unspecified)	0	52 (43-92)	46.9 (48-NR)	NR	NR	NR
Maio et al[34], 2017	382	Tremelimumab	Malignant mesothelioma	283 (74)	66 (60-72)	19.61 (0.23-26.48)	7 (2)	3 (< 1%)	NR
Mateos et al[35], 2019	125	Pembrolizumab plus pomalidomide and dexamethasone	Multiple myeloma	77 (62)	65 (60-72)	25.7 (IQR 25.6-25.8)	NR	NR	NR
Motzer et al[36], 2019	550	Nivolumab plus ipilimumab	Advanced renal cell carcinoma	NR	NR	2 (1-3)	NR	NR	NR
Sarocchi et al[37], 2018	59	Nivolumab	Advanced non-small cell lung cancer	41 (NR)	69 (44-81)	8.1 (IQR 4.5-10.9)	NR	NR	51 (86)
Scherpereel et al[6], 2019	63	Nivolumab or nivolumab plus ipilimumab	Relapsed malignant pleural mesothelioma	47 (75)	72.3 (32.5-87)	32.4 (IQR 13.4-36.3)	NR	NR	34 (54)
Tawbi et al[38], 2018	94	Nivolumab plus ipilimumab	Melanoma with brain metastases	65 (69)	59 (22-81)	NR	NR	NR	NR
Ueno et al[39], 2019a	30	Nivolumab alone	Unresectable or recurrent biliary tract cancer	NR	NR	20.1 (IQR 19.6-20.3)	NR	NR	NR
Ueno et al[39], 2019b	30	Nivolumab in combination with cisplatin	Unresectable or recurrent biliary tract cancer	NR	NR	14 (6-NR)	NR	NR	NR
Usmani et al[40], 2019a	151	Pembrolizumab	Multiple myeloma	70 (46)	74 (70-79)	5.1 (IQR 3.4-7)	NR	NR	NR
Usmani et al[40], 2019b	150	Lenalidomide	Multiple myeloma	71 (47)	74 (70-78	8.2 (IQR 7-14)	NR	NR	NR
Wrangle et al[41], 2018	21	ALT-803, an IL-15 superagonist, in combination with nivolumab	Metastatic non-small cell lung	15 (71)	55 (46-67)	6.6 (IQR 3.4-9.6)	NR	NR	12 (57)
Yang et al[42], 2018a	42	Preoperative chemotherapy	Non-small cell lung cancer	21 (50)	NR	6.6 (IQR 3.4-9.6)	NR	7 (17)	NR
Yang et al[42], 2018b	13	Ipilimumab	Non-small cell lung cancer	5 (38)	NR	6.9 (IQR 5.5-12.0)	NR	3 (23)	NR

ICI: Immune checkpoint inhibitor; NR: Not report; IQR: Inter-quartile range.