Influenza vaccination and myocarditis among patients receiving immune checkpoint inhibitors

Awadalla, Magid; Golden, Doll Lauren Alexandra; Mahmood, Syed S.; Alvi, Raza M.; Mercaldo, Nathaniel D.; Hassan, Malek Z. O.; Banerji, Dahlia; Rokicki, Adam; Mulligan, Connor; Murphy, Sean P. T.; Jones-O’Connor, Maeve; Cohen, Justine V.; Heinzerling, Lucie M.; Armanious, Merna; Sullivan, Ryan J.; Damrongwatanasuk, Rongras; Chen, Carol L.; Gupta, Dipti; Kirchberger, Michael C.; Moslehi, Javid J.; Shah, Sachin P.; Ganatra, Sarju; Thavendiranathan, Paaladinesh; Rizvi, Muhammad A.; Sahni, Gagan; Lyon, Alexander R.; Tocchetti, Carlo G.; Mercurio, Valentina; Thuny, Franck; Ederhy, Stephane; Mahmoudi, Michael; Lawrence, Donald P.; Groarke, John D.; Nohria, Anju; Fradley, Michael G.; Reynolds, Kerry L.; Neilan, Tomas G.

doi:10.1186/s40425-019-0535-y

Table 3 Comparison of Myocarditis cases with and without Flu vaccination (FV)

From: Influenza vaccination and myocarditis among patients receiving immune checkpoint inhibitors

	FV (n = 25)	No FV (n = 76)	P Value
Age at start of ICI, yrs	69 ± 8	66 ± 20	0.60
Male	17 (68)	56 (74)	0.58
CV risk factors
Current or prior smoking	10 (48)	30 (47)	0.95
Hypertension	14 (58)	45 (60)	0.89
Diabetes mellitus	7 (30)	15 (21)	0.36
No CV risk factors	4 (16)	19 (25)	0.35
Coronary artery disease	3 (15)	9 (13)	0.73
Stroke	1 (5)	6 (8)	1.00
Heart failure	1 (5)	4 (6)	1.00
COPD	5 (28)	7 (10)	0.12
Obstructive sleep apnea	0	6 (9)	0.60
Chronic kidney disease^a	2 (11)	7 (10)	1.00
Body mass index, kg/m²	28 ± 5	28 ± 7	0.90
Primary cancer type
Head and neck	0	5 (7)	0.33
Hodgkin’s lymphoma	0	2 (3)	1.00
Melanoma	12 (48)	32 (42)	0.61
Lung cancer	6 (24)	11 (14)	0.35
Pancreatic	2 (8)	0	0.06
Renal cell carcinoma	2 (8)	4 (5)	0.64
Glioblastoma	0	2 (3)	1.00
Other	3 (12)	20 (26)	0.18
Prior chemotherapy or radiation
Radiation	4 (16)	25 (33)	0.11
Anthracyclines	1 (4)	5 (7)	1.00
Cyclophosphamide	1 (4)	1 (1)	0.44
Gemcitabine	2 (8)	3 (4)	0.60
Taxanes	2 (8)	4 (5)	0.64
Carboplatin	2 (8)	6 (8)	1.00
VEGF Inhibitors	0	1 (1)	1.00
Single agent vs. combined ICI
Combination	8 (32)	20 (26)	0.61
Monotherapy	17 (68)	56 (74)	0.61
Combined ICI
Ipilimumab + nivolumab	8 (32)	16 (21)	0.27
Ipilimumab + pembrolizumab	0	1 (1)	1.00
Tremelimumab + avelumab	0	1 (1)	1.00
Tremelimumab + durvalumab	0	2 (3)	1.00
Monotherapy ICI ^b
Pembrolizumab (anti-PD1)	7 (28)	28 (37)	0.42
Nivolumab (anti-PD1)	7 (28)	18 (24)	0.66
Ipilimumab (anti-CTLA4)	2 (8)	4 (5)	0.64
Tremelimumab (anti-CTLA4)	1 (4)	0	0.25
Atezolizumab (anti-PDL1)	0	6 (8)	0.33
Avelumab (anti-PDL1)	0	0	1.00
Durvalumab (anti-PDL1)	0	0	1.00
Overall types of ICI
Any anti-PD1	22 (88)	63 (83)	0.75
Any anti-CTLA4	11 (44)	24 (32)	0.33
Any anti-PDL1	0	9 (12)	0.11
Days of follow-up [IQR]	223 [111, 324]	162 [86, 364]	0.32
Other immune side effects during treatment ^c
No other immune side effects	16 (64)	34 (45)	0.10
Hypophysitis/pituitary/adrenal	1 (4)	5 (7)	1.00
Pneumonitis	3 (12)	26 (36)	0.03
Hepatitis	1 (4)	7 (9)	0.68
Colitis	2 (8)	7 (9)	1.00
Dermatitis	0	6 (8)	0.33
Neurological	1 (4)	10 (13)	0.28
Gastritis	0 (0)	3 (4)	0.57
Myocarditis presentation ^c
Chest pain	15 (60)	50 (66)	0.60
Shortness of breath	6 (25)	21 (28)	0.75
Orthopnea	6 (26)	18 (24)	0.86
Paroxysmal nocturnal dyspnea	2 (9)	7 (9)	1.00
Fatigue	8 (40)	27 (46)	0.65
Admission examination
Jugular venous distension	8 (32)	24 (32)	1.00
Crackles on lung exam	8 (32)	36 (47)	0.25
Admission vitals
Heart rate, beats/min	92 ± 16	89 ± 24	0.67
Systolic blood pressure, mmHg	126 ± 17	126 ± 21	0.89
Diastolic blood pressure, mmHg	70 ± 10	72 ± 11	0.48
Respiratory rate, rate, min	19 ± 2	22 ± 14	0.38
Oxygen requirement and delivery ^d
Room air	13 (72)	51 (75)	0.61
Nasal cannula	5 (28)	13 (19)	0.61
Intubated	0	4 (6)	0.61
Echocardiography, myocarditis admission
LVEF^e, %	46 ± 15	50 ± 16	0.28
LVIDD, mm	45 ± 11	48 ± 6	0.15
Admission cardiac enzymes
Troponin T, ng/ml	0.12 [0.02,0.47]	0.40 [0.11,1.26]	0.02
BNP or NT-pro BNP, pg/ml	568 [421,987]	600 [215,4275]	0.82
Outcomes: MACE ^f
Cumulative MACE	6 (24)	45 (59)	0.002
Complete heart block	2 (9)	14 (19)	0.35
Cardiogenic shock	2 (9)	15 (20)	0.35
Cardiac arrest	2 (9)	13 (17)	0.51
Cardiovascular death	4 (36)	28 (72)	0.04

Values are mean ± SD or n (%), or median [interquartile range]. ^aChronic kidney disease = glomerular filtration rate < 60 ml/min/1.73 m². ^bIf most recent ICI therapy was monotherapy. ^cCan include more than 1. ^dOf available cases (18 vaccinated, 69 unvaccinated).^eAll vaccinated cases [25] and 74 of the 76 unvaccinated cases had an admission echocardiogram. ^fCases may have had more than one MACE, but only first event encountered was included in analysis. CV cardiovascular, ICI immune checkpoint inhibitors, anti-CTLA4 anti-cytotoxic T-lymphocyte-associated protein 4, anti-PD1 anti-programmed cell death protein 1, anti-PDL1 anti-programmed death-ligand 1, LVEF left ventricular ejection fraction, LVIDD left ventricular internal dimension diameter, BNP brain natriuretic peptide, NT- pro BNP N-terminal pro BNP

Back to article page