Table 2.
Univariate and multivariate analysis of factors affecting outcome for all patients treated with immunotherapy agents (TMB low or intermediate vs. high) (N = 151)*
| Variable | Group (N) | PR/CR N (%) | OR (95% CI)1 | P –value univariate (PR/CR)2 | P-value multivariate (PR/CR) | Median PFS (mos)3 | HR (95% CI) (PFS)1 | P-value univariate (PFS)4 | P-value multivariate (PFS) | Median OS (mos)3 | HR (95% CI) (OS)1 | P-value univariate (OS)4 | P-value multivariate (OS) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age | ≤60 years (N = 78) | 20 (26%) | 0.66 (0.32–1.33) | 0.2873 | 4.0 | 1.12 (0.77–1.63) | 0.5396 | 28.4 | 1.03 (0.61–1.72) | 0.9165 | |||
| >60 years (N = 73) | 25 (34%) | 1.51 (0.75–3.14) | 5.7 | 0.89 (0.61–1.29) | 25.4 | 0.97 (0.58–1.63) | |||||||
| Gender | Men (N = 93) | 33 (36%) | 2.11 (0.97–4.57) | 0.0675 | 0.235 | 5.8 | 0.70 (0.47–1.03) | 0.0572 | 0.362 | 28.4 | 0.88 ().51–1.50) | 0.6204 | |
| Women (N = 58) | 12 (21%) | 0.47 (0.22–1.03) | 3.6 | 1.44 (0.97–2.12) | 16.3 | 1.14 (0.67–1.95) | |||||||
| Ethnicity | Caucasian (N = 111) | 38 (34%) | 2.45 (0.99–6.29) | 0.0685 | 0.604 | 5.9 | 0.58 (0.36–0.92) | 0.0066 | 0.983 | 28.4 | 0.65 (0.35–1.20) | 0.1192 | |
| Hispanic (N = 18) | 3 (17%) | 0.43 (0.13–1.57) | 0.2745 | 2.6 | 1.38 (0.73–2.61) | 0.2543 | 15.6 | 1.46 (0.64–3.30) | 0.2927 | ||||
| Asian (N = 9) | 1 (11%) | 0.28 (0.02–1.94) | 0.2808 | 2.0 | 2.61 (0.86–7.90) | 0.0063 | 0.083 | Not reached (median f/u 3.4 mos) | 1.84 (0.49–7.01) | 0.2265 | |||
| African American (N = 9) | 3 (33%) | 1.19 (0.31–4.45) | 1.0000 | 3.9 | 1.30 (0.55–3.07) | 0.5002 | Not reached (median f/u 6.5 mos) | 1.26 (0.35–4.60) | 0.6916 | ||||
| Other (N = 4) | 0 (9%) | 0 (0–2.40) | 0.3181 | 4.1 | 1.54 (0.45–5.23) | 0.3902 | 38.33 | 1.02 (0.25–4.27) | 0.9730 | ||||
| Tumor Type | Melanoma (N = 52) | 26 (50%) | 3.68 (1.71–7.82) | 0.0007 | 0.562 | 9.3 | 0.36 (0.25–0.51) | <0.0001 | 0.035 | Not reached (median f/u of 15.6 mos) | 0.26 (0.16–0.43) | <0.0001 | 0.006 |
| NSCLC (N = 36) | 7 (19%) | 0.49 (0.19–1.23) | 0.1460 | 2.8 | 2.00 (1.21–3.27) | 0.0007 | 0.992 | 8.0 | 1.90 (0.97–3.72) | 0.0213 | 0.794 | ||
| Other tumors5 (N = 63) | 12 (19%) | 0.39 (0.18–5.51) | 0.0187 | 0.301 | 2.9 | 1.67 (1.12–2.50) | 0.0056 | 0.992 | 11.2 | 2.13 (1.23–3.69) | 0.0022 | 0.794 | |
| TMB | Low to Intermediate (N = 113) | 23 (20%) | 0.19 (0.09–0.41) | 0.0001 | <0.001 | 3.3 | 2.98 (2.02–4.41) | <0.0001 | <0.001 | 16.3 | 3.03 (1.72–5.33) | 0.0036 | 0.016 |
| High (N = 38) | 22 (58%) | 5.38 (2.44–11.58) | 12.8 | 0.34 (0.23–0.50) | Not reached (median f/u of 10.5 mos) | 0.33 (0.19–0.58) | |||||||
| Type of immunotherapy | Anti-PD-1/PD-L1 monotherapy (N = 102) | 21 (21%) | 0.27 (0.13–0.58) | 0.0006 | 0.743 | 3.3 | 2.41 (1.65–3.50) | <0.0001 | 0.588 | 15.7 | 2.74 (1.63–4.59) | 0.0005 | 0.820 |
| Anti-CTLA4 alone (N = 15) | 2 (13%) | 0.33 (0.07–1.40) | 0.2329 | 4.7 | 1.08 (0.58–2.01) | 0.7957 | 28.4 | 0.87 (0.39–1.95) | 0.7529 | ||||
| High dose IL2 (N = 9) | 5 (56%) | 3.19 (0.88–10.72) | 0.1270 | 37.0 | 0.40 (0.23–0.71) | 0.0146 | 0.070 | Not reached (median f/u of 34.6 mos) | 0.37 (0.17–0.80) | 0.0614 | 0.284 | ||
| Anti-CTLA4/Anti-PD-1/PD-L1 (N = 17) | 13 (77%) | 10.36 (3.05–30.18) | <0.0001 | 0.004 | Not reached (median f/u 9.2 mos) | 0.27 (0.16–0.44) | 0.0006 | 0.024 | Not reached (median f/u of 16.3 mos) | 0.20 (0.10–0.40) | 0.0107 | 0.172 | |
| Other immunotherapy6 (N = 8) | 4 (50%) | 2.49 (0.69–8.82) | 0.2392 | 8.9 | 0.77 (0.32–1.87) | 0.6044 | Not reached (median f/u of 5.5 mos) | 0.81 (0.23–2.92) | 0.7694 |
All univariate P values of ≤0.1 were included in the multivariate analysis. For a similar analysis by TMB low vs. intermediate to high, see Supplemental Table 4.
Odds Ratio (OR) >1.0 implies higher chance of response; Hazard Ratio (HR) <1.0 implies less chance of progression or death
Calculated using Fisher’s exact test
All medians for PFS and OS calculated by Kaplan Meier
Calculated using log-rank (Mantel-Cox) test
Other tumors: Adrenal carcinoma (n=1), appendix adenocarcinoma (n=1), basal cell carcinoma (n=2), bladder transitional cell carcinoma (n=4), breast cancer (n=3), cervical cancer (n=2), colon adenocarcinoma (n=5), cutaneous squamous cell carcinoma (n=8), hepatocellular carcinoma (n=3), head and neck (n=13), Merkel cell carcinoma (n=2), ovarian carcinoma (n=2), pleural mesothelioma (n=1), prostate cancer (n=1), renal cell carcinoma (n=6), sarcoma (n=3), thyroid cancer (n=3), unknown primary squamous cell carcinoma (n=2), and urethral squamous cell carcinoma (n=1)
Other immunotherapy: OX40 (n=3), anti-CD73 (n=1), Talimogene laherparepvec (n=2), OX40+anti-PD-L1 (n=1), and IDO+anti-PD-1/PD-L1 (n=1)
Abbreviations: CI = confidence interval; CR = complete response; CTLA4 = cytotoxic T-lymphocyte associated protein 4; HR = hazard ratio; IL2 = interleukin 2; OR = odds ratio; OS = overall survival; PD-1 = programmed death receptor-1; PD-L1 programmed death receptor-ligand 1; PD = progressive disease: PFS = progression free survival; PR = partial response; TMB = tumor mutational burden