Table 2

Clinical outcomes of patients in validation cohort treated with ipilimumab/nivolumab are evaluated by different gene signatures and by immune checkpoint status

Variable	Category	n	Comparison	ORR			OS			PFS
Variable	Category	n	Comparison	OR	CI low	CI high	HR	CI low	CI high	HR	CI low	CI high
Five gene panel (FOXP3, CCR4, KLRK1, ITK, TIGIT)	High	23	High vs not high	1.35	0.42	4.38	1.50	0.58	3.89	0.96	0.51	1.83
Five gene panel (FOXP3, CCR4, KLRK1, ITK, TIGIT)	Not high	39	High vs not high	1.35	0.42	4.38	1.50	0.58	3.89	0.96	0.51	1.83
Cell proliferation	High	3	High vs poor	1.67	0.12	24.15	6.36	0.95	42.84	4.55	1.11	18.76
	Moderate	15	Moderate vs poor	1.26	0.34	4.64	2.90	1.05	7.99	1.49	0.72	3.08
	Poor	44	High vs moderate	1.32	0.08	21.21	2.20	0.36	13.27	3.05	0.74	12.60
TIGS (immunogenicity)	Strong	27	Strong vs weak	0.53	0.13	2.16	0.99	0.27	3.65	1.30	0.61	2.78
	Moderate	19	Moderate vs weak	0.43	0.09	2.04	3.28	0.90	11.96	1.27	0.55	2.97
	Weak	16	Strong vs moderate	1.21	0.31	4.73	0.30	0.10	0.92	1.02	0.48	2.15
IMDC risk group	Favorable	15	Favorable vs poor	0.36	0.05	2.70	0.12	0.02	0.68	0.54	0.19	1.51
	Intermediate	40	Intermediate vs poor	0.54	0.08	3.51	0.43	0.13	1.43	0.76	0.31	1.91
	Poor	7	Favorable vs intermediate	0.67	0.17	2.59	0.27	0.06	1.28	0.70	0.32	1.52
PD-L1 (IHC)	High	21	High vs not high	1.31	0.42	4.15	1.57	0.63	3.89	0.79	0.42	1.50
PD-L1 (IHC)	Not high	41	High vs not high	1.31	0.42	4.15	1.57	0.63	3.89	0.79	0.42	1.50
PD-L1 (RNA)	High	13	High vs not high	1.07	0.25	4.54	2.05	0.65	6.45	0.79	0.33	1.89
PD-L1 (RNA)	Not high	49	High vs not high	1.07	0.25	4.54	2.05	0.65	6.45	0.79	0.33	1.89
CTLA4 (RNA)	High	13	High vs not high	2.53	0.63	10.16	0.86	0.26	2.80	0.66	0.31	1.43
CTLA4 (RNA)	Not high	49	High vs not high	2.53	0.63	10.16	0.86	0.26	2.80	0.66	0.31	1.43
TMB (high=upper 20%)	High	13	High vs not high	0.97	0.22	4.28	1.01	0.28	3.62	1.39	0.65	3.00
TMB (high=upper 20%)	Not high	49	High vs not high	0.97	0.22	4.28	1.01	0.28	3.62	1.39	0.65	3.00
Entire validation cohort		62

Logistic regression objective response rate OR and Cox models for overall survival HR, and progression free survival HR for individual variables are shown. Logistic regression and Cox models a adjusted for sex, stage at diagnosis, ECOG (Eastern Cooperative Oncology Group) performance status at ipilimumab/nivolumab treatment, and time from diagnosis to ipilimumab/nivolumab of greater or less than 1 year.
CTLA-4, cytotoxic T-lymphocytes-associated protein 4; IHC, immunohistochemistry; IMDC, International Metastatic RCC Database Consortium; PD-L1, programmed death-ligand 1; TIGS, tumor immunogenic signature; TMB, tumor mutational burden.