Patterns of Neurological Adverse Events Among a Retrospective Cohort of Patients Receiving Immune Checkpoint Inhibitors

Figures & data

Table 1. Patient characteristics for the entire cohort stratified by adverse event type.

	Total (N = 3,137)	CNS NAE (n = 23)	PNS NAE (n = 31)	Other irAE (n = 1,122)	None (n = 1,961)
Age (years), mean (std)	63.3 (12.0)	62.7 (9.1)	57.2 (14.0)	64.4 (11.8)	62.8 (12.2)
Missing	32	0	0	3	26
Sex (female)	1243 (40.03%)	7 (58.33%)	7 (41.18%)	297 (41.89%)	769 (39.74%)
Race
White/Caucasian	2653 (85.44%)	11 (91.67%)	14 (82.35%)	630 (88.86%)	1618 (83.62%)
Black/African–American	361 (11.63%)	1 (8.33%)	2 (11.76%)	55 (7.76%)	260 (13.44%)
Other	91 (2.93%)	0 (0.00%)	1 (5.88%)	24 (3.39%)	57 (2.95%)
Missing	32	0	0	3	26
BMI – categorical
Underweight	365 (11.76%)	1 (8.33%)	1 (5.88%)	47 (6.64%)	279 (14.43%)
Normal	1249 (40.25%)	3 (25.00%)	6 (35.29%)	261 (36.86%)	795 (41.11%)
Overweight	784 (25.27%)	3 (25.00%)	7 (41.18%)	200 (28.25%)	454 (23.47%)
Obese	705 (22.72%)	5 (41.67%)	3 (17.65%)	200 (28.25%)	406 (20.99%)
Comorbidities
Neurologic	323 (10.30%)	5 (21.74%)	1 (3.23%)	100 (8.91%)	217 (11.07%)
Visual impairment	836 (26.65%)	6 (26.09%)	9 (29.03%)	316 (28.16%)	505 (25.75%)
Auditory impairment	365 (11.64%)	1 (4.35%)	3 (9.68%)	150 (13.37%)	211 (10.76%)

Categorical variables reported as count and frequency, missing values excluded from percentages.

Continuous variables reported as mean and standard deviation.

Race was self-identified and reported by the patient.

Neurological comorbidities include: Cerebrovascular accident, transient ischemic attack, hemiplegia, dementia, other.

CNS: Central nervous system; irAE: Immune-related adverse event; NAE: Neurological adverse event; PNS: Peripheral nervous system.

Table 2. Adverse events and sub-types by tumor primary.

	Total (N = 3137)	CNS NAE^†^,^‡ (n = 23)	PNS NAE^† (n = 31)	Other irAE (n = 1122)	None (n = 1961)
Tumor primary
Lung	1406 (44.82%)	3 (13.04%)	11 (35.48%)	440 (39.22%)	952 (48.52%)
Melanoma	446 (14.22%)	9 (39.13%)	8 (25.81%)	256 (22.82%)	173 (8.82%)
Renal	196 (6.25%)	6 (26.09%)	5 (16.13%)	90 (8.02%)	95 (4.84%)
Other	1089 (34.71%)	5 (21.74%)	7 (22.58%)	336 (29.95%)	742 (37.79%)

† Significant (p < 0.05) compared with “None”.

‡ Significant (p < 0.05) compared with “Other”.

All tests performed using Fisher’s exact test.

‘Other Tumor primary’ includes: breast, cervical, cutaneous squamous, endometrial, esophageal, gastric, hepatocellular, Hodgkin lymphoma, Merkel cell, urothelial.

CNS: Central nervous system; irAE: Immune-related adverse event; NAE: Neurological adverse event; PNS: Peripheral nervous system.

Table 3. Exploratory modeling, stratified by event type.

CNS NAE		PNS NAE
Variable	OR (95% CI)	Variable	OR (95% CI)
Tumor primary (reference Other)		Tumor primary (reference Other)
Lung	0.49 (0.12–2.05)	Lung	1.17 (0.45–3.03)
Melanoma	3.95 (1.31–11.95)	Melanoma	3.44 (1.22–9.71)
Renal Cell Carcinoma	6.44 (1.92–21.58)	Renal Cell Carcinoma	4.66 (1.45–15.02)
Comorbidities		Comorbidities
Neurological	2.96 (1.05–8.36)	Neurological	4.77 (0.59–38.28)
Obesity	2.11 (0.90–4.95)	Irritable Bowel Disease	0.26 (0.04–1.94)
Cardiovascular disease	0.53 (0.20–1.39)	Obesity	0.20 (0.05–0.86)
		Psychiatric	1.80 (0.87–3.71)
		Peptic Ulcer Disease	3.76 (1.10–12.88)

Neurological comorbidities include cerebrovascular accident – transient ischemic attack – hemiplegia – dementia – and others.

Cardiovascular comorbidities include coronary vascular disease – prior myocardial infarction – peripheral arterial disease.

Peptic ulcer disease comorbidity includes any history of treatment.

Psychiatric comorbidity includes requiring psychiatric consult – medication – or other treatment.

‘Other tumor primary’ includes: breast, cervical, cutaneous squamous, endometrial, esophageal, gastric, hepatocellular, Hodgkin lymphoma, Merkel cell, urothelial.

CNS: Central nervous system; irAE: Immune-related adverse event; NAE: Neurological adverse event; PNS: Peripheral nervous system.

Figure 1. Kaplan-Meier plot for time to each neurological event by severity and type.

Table 4. Survival data stratified by event type and grade.

	Grade 1 or 2			Grade 3 or 4
	CNS NAE (n = 12)	PNS NAE (n = 17)	Other irAE (n = 712)	CNS NAE (n = 11)	PNS NAE (n = 14)	Other irAE (n = 410)	None (n = 1961)
Time ICI to irAE (months)	1.1 (0.7, 4.7)	2 (0.9, 4.2)	2.5 (0.9, 5.7)	1.8 (1.2, 3.3)	1.5 (0.7, 9.3)	1.6 (0.7, 4.2)	NA

Continuous variables reported as median [IQR].

CNS: Central nervous system; irAE: Immune-related adverse event; ICI: Immune checkpoint inhibitor; NAE: Neurological adverse event; PNS: Peripheral nervous system.