Retrospective Study
Copyright
©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2022; 28(39): 5750-5763
Published online Oct 21, 2022. doi: 10.3748/wjg.v28.i39.5750
Table 1 Baseline characteristics of patients with immune checkpoint inhibitor use
Clinical variables All patients (n = 128) Patients with IMC (n = 64) Patients without IMC (n = 64) P value Age, yr (mean ± SD)1 66.6 (± 11.5) 67.4 (± 11.7) 65.8 (± 11.3) 0.420 Sex1 Male, n (%) 74 57.81% 37 57.81% 37 57.81% 1.000 Female, n (%) 54 42.19% 27 42.19% 27 42.19% Race White, n (%) 102 79.69% 52 81.25% 50 78.13% 0.660 Black, n (%) 4 3.13% 2 3.13% 2 3.13% 1.000 Asian, n (%) 9 7.03% 4 6.25% 5 7.81% 0.730 Type of malignancy1 Melanoma, n (%) 66 51.56% 33 51.56% 33 51.56% 1.000 RCC, n (%) 15 11.72% 8 12.50% 7 10.94% 0.783 NSCLC, n (%) 12 9.38% 6 9.38% 6 9.38% 1.000 Sarcoma, n (%) 11 8.59% 5 7.81% 6 9.38% 0.752 Head and neck SCC, n (%) 7 5.47% 3 4.69% 4 6.25% 0.697 Other, n (%) 17 13.28% 9 14.06% 8 12.50% 0.795 Stage IV malignancy, n (%) 114 89.07% 56 87.50% 58 90.63% 0.778 Type of immune checkpoint inhibitor1 Ipilimumab plus nivolumab, n (%) 48 37.50% 24 37.50% 24 37.50% 1.000 Ipilimumab, n (%) 22 17.19% 11 17.19% 11 17.19% 1.000 Nivolumab, n (%) 12 9.38% 6 9.38% 6 9.38% 1.000 Pembrolizumab, n (%) 38 29.69% 19 29.69% 19 29.69% 1.000 Atezolizumab, n (%) 8 6.25% 4 6.25% 4 6.25% 1.000 Number of Infusionsa (mean ± SD)1 6.91 (± 8.40) 6.09 (± 7.20) 7.73 (± 9.40) 0.268 Dose of ICI (mg/kg) (mean ± SD) 2.47 (± 1.30) 2.63 (± 1.60) 2.31 (± 1.00) 0.318 Prior ICI use1 19 14.84% 10 15.63% 9 14.06% 0.500 Medical history, n (%) Non-liver, non-upper GI diseaseb , n (%) 28 21.88% 18 28.13% 10 15.63% 0.087 Personal history of autoimmune diseaseb , n (%) 30 23.44% 20 31.25% 10 15.63% 0.037 Prior irAEb , n (%) 8 12.50% 7 10.90% 1 1.56% 0.062 Family history of autoimmune diseaseb , n (%) 10 7.81% 8 12.50% 2 3.13% 0.048 Prior immune-enhancing therapyb , n (%) 11 8.59% 2 3.13% 9 14.06% 0.027 Prior interferon-γ therapy, n (%) 7 5.47% 1 1.56% 6 9.38% 0.115 Vitamin D use, n (%) 38 29.69% 25 39.06% 13 20.31% 0.020 Smoking (current or prior), n (%) 61 47.66% 33 51.56% 28 43.75% 0.376 NSAID use, n (%) 21 16.41% 10 15.63% 11 17.19% 0.811 Any vaccine, n (%) 25 19.53% 9 14.06% 16 25.00% 0.119 Flu vaccine, n (%) 19 14.84% 7 10.94% 12 18.75% 0.214 Pneumonia vaccine, n (%) 11 8.59% 4 6.25% 7 10.94% 0.344 Other vaccine, n (%) 2 1.56% 1 1.56% 1 1.56% 1.000 Weight at start of ICI (kg) (mean ± SD) 78.1 (± 17.4) 79.4 (± 16.9) 76.8 (± 17.9) 0.396 Medications Steroid at start of ICI, n (%) 20 15.63% 11 17.19% 9 14.06% 0.626 Steroid duration (d) N/A 107.7 (± 164.2) N/A Infliximab use, n (%) N/A 10 15.63% N/A Vedolizumab use, n (%) N/A 1 1.56% N/A Malignancy outcomes Mean PFS (mo) 12.8 (± 15.3) 13.7 (± 14.9) 11.9 (± 15.8) 0.524 PFS > 6 mo, n (%) 63 49.22% 35 54.69% 28 43.75% 0.216 OS (mo) 21.0 (± 18.9) 24.3 (± 19.4) 17.7 (± 18.0) 0.050 OS > 12 mo, n (%) 72.0 56.25% 42 65.63% 30 46.88% 0.025 Death, n (%) 20 15.63% 6 9.38% 14 21.88% 0.051
Table 2 Univariate and multivariate predictors of overall survival > 12 mo among patients with malignancy using immune checkpoint inhibitor (n = 128)
Clinical variables Univariate predictors Multivariate predictors OR 95%CI P value OR 95%CI P value Demographics Age (yr) 1.00 0.97-1.03 0.970 Male 0.92 0.45-1.87 0.822 Female 1.08 0.53-2.20 0.822 Race White 1.37 0.58-3.25 0.473 Black 2.39 0.24-23.6 0.456 Asian 0.97 0.25-3.79 0.965 Other 0.45 0.14-1.45 0.181 Type of malignancy Melanoma 0.87 0.43-1.74 0.688 RCC 1.65 0.53-5.12 0.390 NSCLC 2.52 0.65-9.80 0.181 Sarcoma 0.15 0.03-0.72 0.018 0.17 0.03-0.95 0.043 Head and neck SCC 1.04 0.22-4.84 0.961 Other 1.50 0.52-4.35 0.453 Presence of IMC 2.16 1.06-4.41 0.034 2.81 1.17-6.77 0.021 Presence of high grade IMC 0.47 0.16-1.38 0.167 Stage IV malignancy 0.48 0.14-1.61 0.233 Type of Immune Checkpoint Inhibitor Ipilimumab plus nivolumab 1.32 0.30-5.77 0.714 Ipilimumab 0.74 0.29-1.85 0.517 Nivolumab 1.63 0.46-5.70 0.448 Pembrolizumab 2.93 1.27-6.73 0.011 1.06 0.38-2.98 0.911 Atezolizumab 1.32 0.30-5.77 0.714 Number of ICI infusionsa 1.19 1.08-1.32 0.001 1.23 1.09-1.40 0.001 Dose of ICI (mg/kg) 1.33 0.86-2.05 0.198 Prior ICI use 0.51 0.19-1.37 0.183 Medical history Non-liver, non-upper GI diseaseb 0.87 0.38-2.02 0.747 Personal history of autoimmune diseaseb 1.47 0.63-3.40 0.373 Family history of autoimmune diseaseb 1.03 0.32-4.41 0.804 Prior irAE 2.84 0.31 - 25.9 0.356 Prior immune-enhancing therapyb 0.62 0.18-2.15 0.454 Vitamin D use 0.60 0.28-1.29 0.190 Smoking (current or prior) 0.74 0.37-1.50 0.410 NSAID use 1.04 0.41-2.69 0.928 Any vaccine 0.36 0.14-0.89 0.026 1.03 0.16-6.70 0.972 Flu vaccine 0.22 0.08-0.67 0.007 0.30 0.04-2.31 0.248 Pneumonia vaccine 0.41 0.11-1.48 0.175 Other vaccine 0.77 0.05-12.66 0.858 Weight at start of ICI (kg) 0.99 0.97-1.01 0.207 Medications Steroid at start of ICI 0.74 0.29-1.93 0.541 Steroid duration (d) 1.00 0.997-1.01 0.368 Infliximab use 0.76 0.21-2.77 0.226 Vedolizumab use 1.00 0.99-1.01 1.000
Table 3 Univariate and multivariate predictors of overall survival > 12 mo among patients with immune checkpoint inhibitor colitis (n = 64)
Clinical variables Univariate predictors Multivariate predictors OR 95%CI P value OR 95%CI P value Demographics Age (yr) 0.96 0.92-1.01 0.103 0.93 0.88-0.99 0.023 Male 0.82 0.29-2.32 0.711 Female 1.22 0.43-3.44 0.711 Race White 0.87 0.23-3.27 0.835 Black 1.00 0.90-1.34 0.996 Asian 0.54 0.07-4.10 0.550 Other 1.07 0.97-1.11 0.912 Type of malignancy Melanoma 1.26 0.45-3.51 0.654 RCC 0.51 0.12-2.28 0.381 NSCLC 0.53 0.10-2.85 0.456 Sarcoma 2.38 0.25-22.65 0.451 Head and neck SCC 1.05 0.89-1.10 0.865 Other 5.33 0.62-45.68 0.127 Stage IV malignancy 0.60 0.11-3.26 0.554 Presence of high grade IMC 0.91 0.32-2.57 0.855 Type of immune checkpoint inhibitor Ipilimumab plus nivolumab 0.95 0.31-2.88 0.922 Ipilimumab 0.98 0.25-3.77 0.974 Nivolumab 0.09 0.01-0.83 0.033 0.13 0.01-1.43 0.096 Pembrolizumab 2.74 0.78-9.58 0.114 3.46 0.84-14.19 0.084 Atezolizumab 1.74 0.17-17.73 0.641 Number of ICI infusionsa 0.28 0.04-1.82 0.183 Dose of ICI (mg/kg) 1.88 0.36-9.83 0.457 Prior ICI use 0.46 0.12-1.80 0.265 Medical history Non-liver, non-upper GI diseaseb 1.67 0.51-5.49 0.397 Personal history of autoimmune diseaseb 0.78 0.26-2.31 0.648 Family history of autoimmune diseaseb 0.93 0.20-4.29 0.922 Prior immune-enhancing therapyb 0.55 0.03-9.23 0.678 Prior interferon-g therapy 1.00 0.99-1.10 0.976 Vitamin D use 2.45 0.80-7.46 0.116 2.77 0.75-10.20 0.124 Smoking (current or prior) 1.66 0.59-5.65 0.334 NSAID use 2.55 0.49-13.16 0.265 Any vaccine 5.33 0.62-45.68 0.127 Flu vaccine 1.46 0.26-8.19 0.668 Pneumonia vaccine 1.00 0.99-1.05 0.995 Other vaccine 1.00 1.00-1.01 0.941 Weight at start of ICI (kg) 1.02 0.98-1.05 0.329 Medications Steroid at start of ICI 0.98 0.25-3.77 0.974 Steroid duration (d) 1.00 1.00-1.01 0.736 Infliximab use 2.55 0.49-13.16 0.265 Vedolizumab use 1.00 1.00-1.01 0.936
Table 4 Univariate and multivariate predictors of immune checkpoint inhibitor-mediated colitis among patients using immune checkpoint inhibitor (n = 128)
Clinical variables Univariate predictors Multivariate predictors OR 95%CI P value OR 95%CI P value Demographics Age (yr) 1.01 0.98-1.04 0.417 Male 1.00 0.50-2.02 1.000 Female 1.00 0.50-2.02 1.000 Race White 1.21 0.51-2.88 0.661 Black 1.00 0.14-7.33 1.000 Asian 0.79 0.20-3.07 0.730 Other 0.84 0.27-2.66 0.770 Type of malignancy Melanoma 1.00 0.50-2.00 1.000 RCC 1.16 0.40-3.42 0.784 NSCLC 1.00 0.30-3.28 1.000 Sarcoma 0.82 0.24-2.83 0.753 Head and neck SCC 0.74 0.16-3.44 0.698 Other 1.15 0.41-3.18 0.795 Stage IV malignancy 0.72 0.24-2.22 0.572 Type of Immune Checkpoint Inhibitor Ipilimumab plus nivolumab 1.00 0.49-2.05 1.000 Ipilimumab 1.00 0.40-2.51 1.000 Nivolumab 1.00 0.30-3.28 1.000 Pembrolizumab 1.00 0.47-2.13 1.000 Atezolizumab 1.00 0.24-4.18 1.000 Number of Infusionsa 0.98 0.93-1.02 0.273 Dose of ICI (mg/kg) 1.23 0.82-1.84 0.327 Medical History Non-liver, non-upper GIb 2.11 0.89-5.03 0.091 Autoimmune diseaseb 2.45 1.04-5.78 0.040 1.87 0.74-4.74 0.186 Prior irAE 7.74 0.92-64.82 0.059 Family history of autoimmune diseaseb 4.43 0.90-21.74 0.067 3.98 0.74-21.38 0.107 Prior immune-enhancing therapyb 0.20 0.04-0.95 0.043 0.19 0.04-1.01 0.052 Prior interferon-γ therapy 0.15 0.018-1.31 0.087 Vitamin D use 2.51 1.14-5.54 0.022 2.48 1.01-6.07 0.047 Smoking (current or prior) 1.37 0.68-2.74 0.377 NSAID use 0.89 0.35-2.28 0.811 Any vaccine 0.49 0.20-1.21 0.123 Flu vaccine 0.53 0.19-1.45 0.219 Pneumonia vaccine 0.54 0.15-1.95 0.350 Other vaccine 1.00 0.06-16.34 1.000 Weight at start of ICI (kg) 1.01 0.99-1.03 0.393