Table 5.

Associations Between Biomarker Elevation During ICI Therapy and All-Cause Mortality

	Unadjusted		Adjusteda
	HR (95% CI)	P Value	HR (95% CI)	P Value
ALT
Per 100% increase	0.99 (0.94-1.04)	0.64	1.00 (0.99-1.03)	0.96
Normal	1.00 (reference)		1.00 (reference)
1-2× ULN	0.98 (0.86-1.12)	0.78	0.97 (0.85-1.10)	0.62
>2-3× ULN	1.02 (0.92-1.14)	0.66	1.01 (0.90-1.12)	0.92
>3× ULN	1.11 (1.00-1.2	0.049	1.09 (0.98-1.21)	0.11
AST
Per 100% increase	1.03 (0.96-1.10)	0.38	1.04 (0.98-1.11)	0.18
Normal	1.00 (reference)		1.00 (reference)
1-2× ULN	1.00 (0.86-1.17)	0.98	1.01 (0.87-1.18)	0.87
>2-3× ULN	0.91 (0.81-1.02)	0.10	0.91 (0.81-1.02)	0.11
>3× ULN	0.96 (0.86-1.08)	0.53	0.96 (0.85-1.08)	0.48
LDH
Per 100% increase	1.10 (0.98-1.24)	0.10	1.13 (0.99-1.28)	0.07
Normal	1.00 (reference)		1.00 (reference)
1-2× ULN	1.09 (1.01-1.17)	0.022	1.10 (1.03-1.19)	0.008
>2-3× ULN	1.41 (1.24-1.60)	<0.001	1.41 (1.24-1.60)	<0.001
>3× ULN	1.54 (1.37-1.75)	<0.001	1.58 (1.39-1.78)	<0.001
CPK
Per 100% increase	1.10 (1.01-1.20)	0.035	1.10 (1.01-1.20)	0.029
Normal	1.00 (reference)		1.00 (reference)
1-2× ULN	0.98 (0.87-1.10)	0.75	0.97 (0.86-1.09)	0.56
>2-3× ULN	0.96 (0.87-1.05)	0.34	0.94 (0.86-1.04)	0.22
>3× ULN	1.20 (1.10-1.31)	<0.001	1.20 (1.10-1.31)	<0.001

ULN = upper limit of normal; other abbreviations as in Table 1.

^aModel adjusted for age, sex, BMI, smoking history, history of hypertension, type 2 diabetes, heart failure, and coronary artery disease.