Table 1.
Baseline Characteristics at the Start of the Immune Checkpoint Inhibitors
| All patients | Patients with VTE events within 2 years from ICI start | Patients with no VTE events within 2 years from ICI start | P value | ||||
|---|---|---|---|---|---|---|---|
| Demographics | |||||||
| Number of patients | 2854 | 244 | 2610 | ||||
| Male | 1640 (57.5%) | 130 (53.3%) | 1510(57.9%) | 0.18 | |||
| Age (years) | 64±13 | 63±12 | 65±13 | 0.047 | |||
| Data available (n) | Number (%) | Data available (n) | Number (%) | Data available (n) | Number (%) | ||
| Race | |||||||
| White | 2704 | 2479 (91.7%) | 241 | 216 (89.6%) | 2463 | 2263 (91.9%) | 0.12 |
| Asian | 96 (3.6%) | 11 (4.6%) | 85 (3.5%) | ||||
| Black or African American | 57 (2.1%) | 10 (4.2%) | 47 (1.9%) | ||||
| Hispanic | 29 (0.9%) | 1 (0.4%) | 24 (1.0%) | ||||
| Other | 43 (1.6%) | 3 (1.2%) | 44 (1.6%) | ||||
| Baseline Risk Factors | |||||||
| Hypertension | 2756 | 1356 (49.2%) | 244 | 118 (48.4%) | 2512 | 1238 (48.9%) | 0.78 |
| Diabetes mellitus | 2756 | 433 (15.7%) | 244 | 39 (16.0%) | 2512 | 394 (15.7%) | 0.90 |
| Smoking current or prior | 2756 | 429 (15.6%) | 244 | 27 (15.2%) | 2512 | 392 (15.6%) | 0.92 |
| Chronic kidney disease | 2756 | 327 (11.9%) | 244 | 23 (9.4%) | 2512 | 304 (12.1%) | 0.21 |
| History of myocardial infarction | 2854 | 136 (4.5%) | 244 | 11 (4.5%) | 2598 | 125 (4.8%) | 1.00 |
| History of any coronary revascularization | 2854 | 195 (6.9%) | 244 | 7 (2.9%) | 2598 | 188 (7.2%) | 0.008 |
| History of ischemic stroke | 2854 | 82 (2.9%) | 244 | 6 (2.5%) | 2598 | 76 (2.9%) | 0.84 |
| History of any cardiovascular event | 2854 | 322 (11.3%) | 244 | 20 (8.2%) | 2598 | 302 (11.6%) | 0.11 |
| History of venous thromboembolism | 2854 | 358 (12.5%) | 244 | 45 (18.4%) | 2610 | 313 (12.0%) | 0.004 |
| Khorana Risk score | |||||||
| 0 | 2136 | 779 (36.5%) | 195 | 51 (26.2%) | 1941 | 728 (37.5%) | 0.0014 |
| 1 | 759 (35.5%) | 78(40.0%) | 681 (35.1%) | ||||
| 2 | 428 (20.0%) | 41(21.0%) | 387 (19.9%) | ||||
| 3 | 135 (6.3%) | 19(9.7%) | 116(6.0%) | ||||
| 4 | 33 (1.5%) | 5(2.6%) | 28 (1.4%) | ||||
| 5 | 2 (0.09%) | 1(0.5%) | 1 (0.05%) | ||||
| Baseline Cardiovascular Medications | |||||||
| Angiotensin Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker | 2704 | 612 (22.6%) | 239 | 52 (21.8%) | 2465 | 560 (22.7%) | 0.73 |
| Statins | 2704 | 705 (26.1%) | 243 | 89 (36.6%) | 2515 | 772 (30.1%) | 0.057 |
| Aspirin | 2704 | 578 (21.4%) | 239 | 61 (25.5%) | 2465 | 517 (20.1%) | 0.10 |
| Other anti-platelet | 2704 | 66 (2.4%) | 239 | 3 (1.3%) | 2486 | 63 (2.6%) | 0.21 |
| Any anticoagulation | 2730 | 262 (9.6%) | 244 | 27 (11.1%) | 2486 | 235 (9.5%) | 0.42 |
| Low Molecular Weight Heparin (treatment dosing) | 2730 | 139 (5.1%) | 244 | 21 (8.6%) | 2486 | 116 (4.8%) | 0.014 |
| Direct Oral Anticoagulant | 2730 | 60 (2.2%) | 244 | 4 (1.6%) | 2486 | 56 (2.3%) | 0.82 |
| Warfarin | 2730 | 96 (3.5%) | 244 | 6 (2.5%) | 2486 | 90 (3.6%) | 0.46 |
| Cancer Types | |||||||
| Non-small cell lung | 2754 | 781 (28.4%) | 244 | 82 (33.6%) | 2511 | 699 (27.8%) | 0.056 |
| Melanoma | 778 (28.2%) | 49 (20.1%) | 729 (29.0%) | 0.003 | |||
| Head and neck | 334 (12.1%) | 27 (11.1%) | 307 (12.2%) | 0.59 | |||
| Renal and genitourinary | 174 (6.3%) | 23 (9.4%) | 151 (6.0%) | 0.036 | |||
| Breast | 119 (4.3%) | 11 (4.5%) | 108 (4.3%) | 0.88 | |||
| Gastrointestinal | 109 (3.9%) | 12 (4.9%) | 97 (3.9%) | 0.42 | |||
| Gynecologic | 107 (3.9%) | 11 (4.5%) | 96 (3.8%) | 0.60 | |||
| Non-Hodgkin Lymphoma | 76 (2.7%) | 6 (2.5%) | 70 (2.8%) | 0.76 | |||
| Hepatocellular | 58 (2.1%) | 4 (1.6%) | 54 (2.2%) | 0.60 | |||
| Cholangiocarcinoma | 39 (1.4%) | 2 (0.8%) | 37 (1.5%) | 0.41 | |||
| Pancreatic | 37 (1.3%) | 5 (2.1%) | 32 (1.3%) | 0.32 | |||
| Other | 142 (5.2%) | 12 (4.9%) | 130 (5.2%) | 0.86 | |||
| Prior Cancer Therapies | |||||||
| Radiation therapy | 2756 | 572 (20.8%) | 244 | 51 (20.9%) | 2512 | 521 (20.7%) | 0.93 |
| Anthracyclines | 2723 | 151 (5.5%) | 242 | 15 (6.2%) | 2481 | 136 (5.5%) | 0.64 |
| Tyrosine kinase inhibitors | 2723 | 61 (2.2%) | 242 | 7 (2.9%) | 2481 | 54 (2.2%) | 0.47 |
| 5- Fluorouracil | 2723 | 284 (10.4%) | 242 | 22 (9.1%) | 2481 | 262 (9.6%) | 0.58 |
| Platinum-based chemotherapy | 2723 | 1022 (37.5%) | 242 | 94 (38.8%) | 2481 | 928 (37.4%) | 0.68 |
| Janus kinase Inhibitors | 2723 | 1 (0.04%) | 242 | 0 | 2481 | 1 (0.04%) | 1.00 |
| Tumor necrosis factor inhibitors | 2723 | 11 (0.4%) | 242 | 0 | 2481 | 11 (0.4%) | 0.62 |
| Mitogen-activated protein kinase kinase inhibitor | 2723 | 44 (1.6%) | 242 | 2 (0.84%) | 2481 | 42 (1.7%) | 0.43 |
| Anaplastic lymphoma kinase inhibitor | 2723 | 11 (0.4%) | 242 | 1 (0.41%) | 2481 | 10 (0.40%) | 1.00 |
| Immune Checkpoint Inhibitor Type | |||||||
| Single Therapy | |||||||
| Programmed death-ligand-1 | 2854 | 283 (9.9%) | 244 | 30 (12.3%) | 2610 | 253 (9.7%) | 0.21 |
| Cytotoxic-T-Lymphocyte associated protein 4 | 2854 | 225 (7.9%) | 244 | 14 (5.7%) | 2610 | 211 (8.1%) | 0.22 |
| Programmed death-protein 1 | 2854 | 2147 (75.2%) | 244 | 180 (73.8%) | 2610 | 1968 (75.4%) | 0.58 |
| Cytotoxic-T-Lymphocyte associated protein 4 or programmed death protein 1 | 2854 | 2(0.1%) | 244 | 0 (0%) | 2610 | 2 (0.08%) | 1.00 |
| Combination Therapy | |||||||
| Cytotoxic-T-Lymphocyte associated protein 4/Programmed death protein 1 | 2854 | 197 (6.9%) | 244 | 20 (8.2%) | 2610 | 176 (6.7%) | 0.36 |
| Corticosteroid treatment at start of ICI | 2342 | 417 (17.8%) | 208 | 41 (19.7%) | 2134 | 376 (17.6%) | 0.45 |
| Time from cancer diagnosis to ICI initiation – days (IQR) | 2745 | 652 (195–1972) | 243 | 550 (170–1870) | 2502 | 665 (199–1975) | 0.15 |
| Immune Related Adverse Events (irAE) with ICI Use | |||||||
| Gastrointestinal | 2748 | 500 (18.2%) | 243 | 36 (14.8%) | 2505 | 464 (18.5%) | 0.15 |
| Skin | 2748 | 429 (15.6%) | 243 | 33 (13.6%) | 2505 | 396 (15.8%) | 0.36 |
| Pulmonary | 2748 | 189 (6.9%) | 243 | 26 (10.7%) | 2505 | 163 (6.5%) | 0.014 |
| Hepatic | 2748 | 179 (6.5%) | 243 | 14 (5.8%) | 2505 | 165 (6.6%) | 0.62 |
| Endocrine | 2748 | 175 (6.4%) | 243 | 21 (8.6%) | 2505 | 154 (6.2%) | 0.13 |
| Renal | 2748 | 120 (4.4%) | 243 | 8 (3.3%) | 2505 | 112 (4.5%) | 0.39 |
| Neuromuscular | 2815 | 98 (3.8%) | 241 | 8 (3.3%) | 2574 | 90 (3.5%) | 0.88 |
| Pancreas | 2748 | 61 (2.2%) | 243 | 2 (0.8%) | 2505 | 59 (2.4%) | 0.12 |
| Any of the above adverse events | 2748 | 1179 (42.9%) | 243 | 103 (42.4%) | 2505 | 1076 (43.0%) | 0.86 |
| Corticosteroids use for irAE | 2748 | 734 (26.7%) | 243 | 69 (28.4%) | 2505 | 665 (26.6%) | 0.53 |
| Baseline Clinical Parameters and Lab Values | |||||||
| Data available (n) | Mean±SD | Data available (n) | Mean±SD | Data available (n) | Mean±SD | ||
| Body mass index - (kg/m2) | 2271 | 27.0±6.4 | 206 | 27.0±5.6 | 2065 | 27.0±6.5 | 0.81 |
| Systolic blood pressure (mmHg) | 2297 | 127.6±18.6 | 207 | 126.6±17.0 | 2090 | 127.7±18.7 | 0.40 |
| Hemoglobin (g/dL) | 2599 | 11.9±2.0 | 231 | 11.7± 1.9 | 2368 | 11.9±2.0 | 0.11 |
| Platelets (thousands/uL) | 2598 | 253.8± 113.0 | 230 | 284.1±130.7 | 2368 | 251.0±110.8 | <0.001 |
| High density lipoprotein (mg/dL) | 810 | 50.0±20.0 | 74 | 51.6±20.6 | 736 | 49.8±20.0 | 0.44 |
| Low density lipoprotein (mg/dL) | 785 | 100.0±36.9 | 73 | 107.5±38.4 | 712 | 99.2±36.6 | 0.067 |
| Glomerular filtration rate (mL/min/1.73m2) | 1035 | 68.2±23.9 | 88 | 67.6±23.2 | 947 | 68.3±24.0 | 0.81 |
| Data available (n) | Median (IQR) | Data available (n) | Median (IQR) | Data available (n) | Median (IQR) | ||
| White blood count (thousand/uL) | 2701 | 7.1 (5.5–9.3) | 239 | 7.6(5.7–10.2) | 2462 | 7.1(5.5–9.2) | 0.0081 |