Table 3.
Univariate and multivariate regression models of ICB and combination therapy response in PBRM1 mutated ccRCC patients in MSKCC cohort (n = 189).
| Time-to-treatment failure | Overall survival | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Univariate analysis | Multivariate model | Univariate analysis | Multivariate model | |||||||
| Variable | HR (95% CI) | P value | HR | 95% CI | P value | HR (95% CI) | P value | HR | 95% CI | P value |
| PBRM1 wild type | 1 | Ref. | 1 | Ref. | ||||||
| LOF | 0.73 (0.5–1.07) | 0.112 | 0.85 | 0.57, 1.28 | 0.44 | 1.5 (0.85–2.66) | 0.161 | 1.24 | 0.69, 2.25 | 0.47 |
| Non-LOF | 1.05 (0.67–1.65) | 0.838 | 1.22 | 0.77, 1.94 | 0.4 | 1.05 (0.46–2.4) | 0.914 | 0.88 | 0.36, 2.14 | 0.78 |
| TMB | 0.94 (0.89–0.99) | 0.029 | 0.96 | 0.90, 1.02 | 0.19 | 0.99 (0.9–1.08) | 0.778 | |||
| Age at treatment | 1.29 (0–610.11) | 0.936 | 1.31 (0–56668.63) | 0.96 | ||||||
| Genome doubled | 1.08 (0.74–1.59) | 0.695 | 1.56 (0.89–2.74) | 0.115 | ||||||
| Fraction CNA | 1.46 (0.79–2.71) | 0.227 | 2.04 (0.78–5.35) | 0.144 | ||||||
| CTLA-4 status | 0.155 | 0.376 | ||||||||
| No | 1 | 1 | ||||||||
| Yes | 1.33 (0.9–1.99) | 0.74 (0.38–1.44) | ||||||||
| IMDC risk | 0.211 | <0.001 | ||||||||
| 1, 2 | 1 | 1 | ||||||||
| 3 | 1.35 (0.84–2.17) | 3 (1.59–5.66) | 4.22 | 2.18, 8.17 | <0.001 | |||||
| Drug class | 0.003 | 0.028 | ||||||||
| IO | 1 | 1 | 1 | |||||||
| IO–IO | 1 (0.66–1.54) | 1 | 0.54 (0.27–1.09) | |||||||
| IO-VEGF | 0.55 (0.38–0.8) | 0.54 | 0.38, 0.76 | <0.001 | 0.46 (0.24–0.87) | |||||
| Line of therapy | 0.211 | <0.001 | ||||||||
| >1 | 1 | 1 | 0.27 | 0.15, 0.49 | <0.001 | |||||
| 1 | 0.81 (0.59–1.12) | 0.34 (0.19–0.59) | ||||||||
| BAP1 | 0.842 | 0.702 | ||||||||
| No | 1 | 1 | ||||||||
| Yes | 0.96 (0.64–1.44) | 1.14 (0.59–2.21) | ||||||||
| SETD2 | 0.48 | 0.71 | ||||||||
| No | 1 | 1 | ||||||||
| Yes | 0.88 (0.62–1.26) | 0.9 (0.51–1.59) | ||||||||
P values derived from Cox proportional hazards model. For multivariate model IO and IO/IO were combined into one category. Multivariate model is based on 180 patients with available risk score.