Table 1.
Patient characteristics (N = 155)1
| Variables | All (N=155) |
TTF <2 months (N=49) |
TTF ≥2 months (N=106) |
Odds- ratio * (95% CI) (Univariate) |
p-value * (Univariate) |
Odds- ratio # (95% CI) (Multivariate) |
p-value # (Multivariate) |
p-value § (Bootstrap) |
|---|---|---|---|---|---|---|---|---|
| Age ≤ 65 years | 104 (67.1%) | 32 (65.3%) | 72 (67.9%) | 0.89 (0.44–1.80) | 0.85 | |||
| Age > 65 years | 51 (32.9%) | 17 (34.7%) | 34 (32.1%) | |||||
| Cancer diagnosis | ||||||||
| Melanoma | 51 (32.9%) | 6 (12.2%) | 45 (42.5%) | 0.19 (0.08–0.48) | 0.0002 | 0.12 (0.01–0.74) | 0.02 | 0.004 |
| Non-small cell lung cancer | 38 (24.5%) | 18 (36.7%) | 20 (18.9%) | 2.50 (1.17–5.32) | 0.03 | 1.33 (0.44–4.00) | 0.75 | 0.56 |
| Squamous cell carcinoma of head and Neck | 11 (7.1%) | 4 (8.2%) | 7 (6.6%) | 1.26 (0.39–4.25) | 0.74 | |||
| Cutaneous squamous cell carcinoma | 9 (5.8%) | 0 (0) | 9 (8.5%) | <0.26 (0.02–1.77) ¶ | 0.06 | 0.85 (0–7.36) | 0.91 | 0.001 |
| Renal cell carcinoma | 6 (3.9%) | 3 (6.1%) | 3 (2.8%) | 2.24 (0.50–9.82) | 0.38 | |||
| Colorectal cancer | 5 (3.2%) | 2 (4.1%) | 3 (2.8%) | 1.46 (0.25–7.33) | 0.65 | |||
| Types of immunotherapy | ||||||||
| Anti-PD-1 or PD-L1 | 102 (65.8%) | 39 (79.6%) | 63 (59.4%) | 2.66 (1.19–5.72) | 0.02 | 0.37 (0.05–2.50) | 0.39 | 0.19 |
| Anti-CTLA-4 alone or in combination with anti-PD-1 † | 35 (22.6%) | 5 (10.2%) | 30 (28.3%) | 0.29 (0.12–0.76) | 0.01 | 0.84 (0.12–7.40) | 1.00 | 0.74 |
| High-dose IL2 | 10 (6.5%) | 3 (6.1%) | 7 (6.6%) | 0.92 (0.25–3.66) | >0.9999 | |||
| Investigational agents | 8 (5.2%) | 2 (4.1%) | 6 (5.7%) | 0.71 (0.14–2.95) | >0.9999 | |||
| Genomic alterations | ||||||||
| TP53 | 65 (41.9%) | 24 (49.0%) | 41 (38.7%) | 1.52 (0.78–2.99) | 0.29 | |||
| CDKN2A/B | 46 (29.7%) | 12 (24.5%) | 34 (32.1%) | 0.69 (0.31–1.50) | 0.45 | |||
| TERT | 37 (23.9%) | 7 (14.3%) | 30 (28.3%) | 0.42 (0.16–1.05) | 0.07 | 1.68 (0.43–6.62) | 0.57 | 0.47 |
| BRAF | 28 (18.1%) | 8 (16.3%) | 20 (18.9%) | 0.84 (0.35–1.99) | 0.82 | |||
| LRP1B | 19 (12.3%) | 4 (8.2%) | 15 (14.2%) | 0.54 (0.19–1.67) | 0.43 | |||
| PTEN | 16 (10.3%) | 2 (4.1%) | 14 (13.2%) | 0.28 (0.06–1.14) | 0.10 | 0.26 (0.02–1.54) | 0.19 | 0.06 |
| MYC | 15 (9.7%) | 5 (10.2%) | 10 (9.4%) | 1.09 (0.40–3.20) | >0.9999 | |||
| NF1 | 14 (9.0%) | 1 (2.0%) | 13 (12.3%) | 0.15 (0.01–0.85) | 0.07 | 0.26 (0.01–2.27) | 0.37 | 0.17 |
| PIK3CA | 14 (9.0%) | 6 (12.2%) | 8 (7.5%) | 1.71 (0.54–5.50) | 0.37 | |||
| KRAS | 12 (7.7%) | 3 (6.1%) | 9 (8.5%) | 0.70 (0.20–2.79) | 0.75 | |||
| MLL2 | 12 (7.7%) | 2 (4.1%) | 10 (9.4%) | 0.41 (0.09–1.66) | 0.34 | |||
| NOTCH1 | 11 (7.1%) | 0 (0) | 11 (10.4%) | <0.19 (0.02–1.22) ¶ | 0.02 | 0.55 (0–3.67) | 0.63 | 0.003 |
| NRAS | 11 (7.1%) | 1 (2.0%) | 10 (9.4%) | 0.20 (0.02–1.24) | 0.18 | |||
| ARID2 | 10 (6.5%) | 1 (2.0%) | 9 (8.5%) | 0.22 (0.02–1.46) | 0.17 | |||
| EGFR | 10 (6.5%) | 8 (16.3%) | 2 (1.9%) | 10.2 (2.28–48.3) | 0.002 | 8.36 (1.28–98.5) | 0.02 | 0.004 |
| CTNNB1 | 9 (5.8%) | 3 (6.1%) | 6 (5.7%) | 1.09 (0.29–4.08) | >0.9999 | |||
| APC | 8 (5.2%) | 3 (6.1%) | 5 (4.7%) | 1.32 (0.34–5.29) | 0.71 | |||
| ARID1A | 8 (5.2%) | 2 (4.1%) | 6 (5.7%) | 0.71 (0.14–2.95) | >0.9999 | |||
| ASXL1 | 8 (5.2%) | 1 (2.0%) | 7 (6.6%) | 0.29 (0.03–1.74) | 0.44 | |||
| BRCA2 | 8 (5.2%) | 2 (4.1%) | 6 (5.7%) | 0.71 (0.14–2.95) | >0.9999 | |||
| CCND1 | 8 (5.2%) | 2 (4.1%) | 6 (5.7%) | 0.71 (0.14–2.95) | >0.9999 | |||
| FGFR1 | 8 (5.2%) | 4 (8.2%) | 4 (3.8%) | 2.27 (0.63–8.02) | 0.26 | |||
| PTCH1 | 8 (5.2%) | 1 (2.0%) | 7 (6.6%) | 0.29 (0.03–1.74) | 0.44 | |||
| SETD2 | 8 (5.2%) | 2 (4.1%) | 6 (5.7%) | 0.71 (0.14–2.95) | >0.9999 | |||
| ATM | 7 (4.5%) | 2 (4.1%) | 5 (4.7%) | 0.86 (0.17–4.25) | >0.9999 | |||
| NOTCH2 | 7 (4.5%) | 2 (4.1%) | 5 (4.7%) | 0.86 (0.17–4.25) | >0.9999 | |||
| RB1 | 7 (4.5%) | 3 (6.1%) | 4 (3.8%) | 1.66 (0.40–6.38) | 0.68 | |||
| RET | 7 (4.5%) | 3 (6.1%) | 4 (3.8%) | 1.66 (0.40–6.38) | 0.68 | |||
| SMAD4 | 7 (4.5%) | 2 (4.1%) | 5 (4.7%) | 0.86 (0.17–4.25) | >0.9999 | |||
| BAP1 | 6 (3.9%) | 3 (6.1%) | 3 (2.8%) | 2.24 (0.50–9.82) | 0.38 | |||
| CREBBP | 6 (3.9%) | 0 (0) | 6 (5.7%) | <0.42 (0.04–3.24) ¶ | 0.18 | |||
| ERBB2 | 6 (3.9%) | 2 (4.1%) | 4 (3.8%) | 1.09 (0.20–4.79) | >0.9999 | |||
| FAT1 | 6 (3.9%) | 1 (2.0%) | 5 (4.7%) | 0.42 (0.04–3.24) | 0.67 | |||
| GNAS | 6 (3.9%) | 1 (2.0%) | 5 (4.7%) | 0.42 (0.04–3.24) | 0.67 | |||
| MCL1 | 6 (3.9%) | 2 (4.1%) | 4 (3.8%) | 1.09 (0.20–4.79) | >0.9999 | |||
| MDM2/4 | 6 (3.9%) | 6 (12.2%) | 0 (0) | >11.9 (1.53–141.6) ¶ | 0.001 | 10.8 (1.88-infinity) | 0.02 | 0.001 |
| PDGFRA | 6 (3.9%) | 1 (2.0%) | 5 (4.7%) | 0.42 (0.04–3.24) | 0.67 | |||
| SOX2 | 6 (3.9%) | 4 (8.2%) | 2 (1.9%) | 4.62 (1.04–24.7) | 0.08 | 1.56 (0.14–22.0) | 1.00 | 0.49 |
| STK11 | 6 (3.9%) | 1 (2.0%) | 5 (4.7%) | 0.42 (0.04–3.24) | 0.67 | |||
| CD274 (PD-L1) | 5 (3.2%) | 0 (0) | 5 (4.7%) | <0.53 (0.04–3.36) ¶ | 0.18 | |||
| DNMT3A | 5 (3.2%) | 4 (8.2%) | 1 (0.9%) | 9.33 (1.46–115.1) | 0.03 | 13.9 (1.11–783.2) | 0.04 | 0.04 |
| ERBB4 | 5 (3.2%) | 0 (0) | 5 (4.7%) | <0.53 (0.04–3.36) ¶ | 0.18 | |||
| FBXW7 | 5 (3.2%) | 3 (6.1%) | 2 (1.9%) | 3.39 (0.67–19.4) | 0.33 | |||
| FGF19 | 5 (3.2%) | 2 (4.1%) | 3 (2.8%) | 1.46 (0.25–7.33) | 0.65 | |||
| FGF3 | 5 (3.2%) | 2 (4.1%) | 3 (2.8%) | 1.46 (0.25–7.33) | 0.65 | |||
| FGF4 | 5 (3.2%) | 2 (4.1%) | 3 (2.8%) | 1.46 (0.25–7.33) | 0.65 | |||
| FGF6 | 5 (3.2%) | 2 (4.1%) | 3 (2.8%) | 1.46 (0.25–7.33) | 0.65 | |||
| JAK2 | 5 (3.2%) | 0 (0) | 5 (4.7%) | <0.53 (0.04–3.36) ¶ | 0.18 | |||
| KDM6A | 5 (3.2%) | 0 (0) | 5 (4.7%) | <0.53 (0.04–3.36) ¶ | 0.18 | |||
| MET | 5 (3.2%) | 2 (4.1%) | 3 (2.8%) | 1.46 (0.25–7.33) | 0.65 | |||
| PBRM1 | 5 (3.2%) | 2 (4.1%) | 3 (2.8%) | 1.46 (0.25–7.33) | 0.65 | |||
| PDCD1LG2 | 5 (3.2%) | 0 (0) | 5 (4.7%) | <0.53 (0.04–3.36) ¶ | 0.18 | |||
| ZNF217 | 5 (3.2%) | 0 (0) | 5 (4.7%) | <0.53 (0.04–3.36) ¶ | 0.18 | |||
| Absolute lymphocyte count (mm3) (N=152) ¥ | ||||||||
| All (N=152) | TTF < 2 months (N=48) | TTF ≥2 months (N=104) | Odds- ratio* | p-value* (Univariate) | ||||
| < 1,000 | 48 (31.6%) | 18 (37.5%) | 30 (28.8%) | 1.48 (0.73–3.09) | 0.35 | |||
| ≥ 1,000 | 104 (68.4%) | 30 (62.5%) | 74 (71.2%) | |||||
| Royal Marsden Hospital score (N=133) ** | ||||||||
| All (N=133) | TTF < 2 months (N=40) | TTF ≥2 months (N=93) | Odds- ratio* | p-value* (Univariate) | ||||
| 0 or 1 | 86 (64.7%) | 22 (55%) | 64 (68.8%) | 0.55 (0.26–1.20) | 0.17 | |||
| 2 or 1 | 47 (35.3%) | 18 (45%) | 29 (31.2%) | |||||
| MD Anderson Cancer Center prognostic score (N=133) ** | ||||||||
| All (N=133) | TTF < 2 months (N=40) | TTF ≥2 months (N=93) | Odds- ratio* | p-value* (Univariate) | ||||
| 0 or 1 | 31 (23.3%) | 7 (17.5%) | 24 (25.8%) | 0.61 (0.24–1.51) | 0.37 | |||
| 2 to 5 | 102 (76.7%) | 33 (82.5%) | 69 (74.2%) | |||||
Odds-ratio and p-value by Fisher’s exact test.
Odds-ratio and p-value by exact conditional logistic regression (multivariate) analysis. Included characteristics with p-value ≤ 0.1 from univariate analysis.
Bootstrapping with multiple logistic regression analysis was conducted on characteristics with p-value ≤ 0.1 from univariate analysis. p-value based on 982 bootstrap samples.
Anti-CTLA-4 alone; N=19, anti-CTLA-4 in combination with ant-PD-1; N=16. Among patients who received anti-CTLA-4 alone, 3 patients had TTF <2 months. Among patients receiving combination of anti-CTLA-4/PD-1, 2 patients had TTF <2 months.
If a variable dichotomized as N versus zero, and the odds ratio was thus zero or infinity, we adjusted the events to be 1 (instead of zero) versus N-1. This produces a numerical odds ratio, which is less than the actual infinite odds ratio. For example, for MDM2/4, where there were N = 6 versus zero patients with TTF<2 versus ≥2 months, the actual odds ratio is infinity. Using the adjustment above, the numeric odds ratio for N = 5 versus one patient is 11.9 and we list it as “>11.9.” The p-value shown is the actual p-value for the unadjusted numbers.
Total of N=152 were tested for lymphocyte count within 4 weeks of starting the immunotherapy.
N=133 were evaluable for Royal Marsden Hospital score and MD Anderson Cancer Center prognostic score. For Royal Marsden Hospital score, each point was counted when albumin was <3.5 (g/dl), LDH > upper limit of normal (175 U/L) and number of organ metastases > 2. For MD Anderson Cancer Center prognostic score, each point was counted when albumin was <3.5 (g/dl), LDH > upper limit of normal (175 U/L), number of organ metastases > 2, gastrointestinal tumor type, and ECOG PS ≥ 1.
Included variables with N ≥ 5.
Abbreviations: CI = confidence interval; IL2 = interleukin-2; TTF = time-to-treatment failure.