Table 1. Associations Between Patient Characteristics, cirAE Features, and Emergence of Any irAE in 358 Patients.
| Characteristic | No. (%) | OR (95% CI) | P valuea | ||
|---|---|---|---|---|---|
| Total cirAE patients (n = 358) | Patients | ||||
| With irAE (n = 177) | Without irAE (n = 181) | ||||
| Age, median (IQR), y | 65 (55-73) | 64 (54-72) | 66 (56-74) | NS | NS |
| Sex | |||||
| Women | 145 (40.5) | 72 (40.7) | 73 (59.7) | NS | NS |
| Men | 213 (59.5) | 105 (49.3) | 108 (50.7) | ||
| Cancer type | |||||
| Melanoma | 150 (41.9) | 113 (63.8) | 37 (20.4) | [Reference] | |
| Lung | 59 (16.5) | 18 (10.2) | 41 (22.7) | 0.15 (0.08-0.32) | <.001 |
| Head or neck | 32 (8.9) | 10 (5.6) | 22 (12.2) | 0.17 (0.07-0.44) | <.001 |
| Gastrointestinal | 34 (9.5) | 12 (6.8) | 22 (12.2) | 0.18 (0.08-0.47) | <.00 |
| Otherb | 83 (23.2) | 24 (13.6) | 59 (32.6) | 0.17 (0.09-0.34) | <.001 |
| Cancer stage, median (IQR) | 4 (3-4) | 4 (3-4) | 4 (3-4) | NS | NS |
| ECOG PMR, median (IQR) | 1 (1-2) | 1 (1-2) | 1 (1-2) | NS | NS |
| Pre-ICI treatments | |||||
| Radiotherapy | 141 (39.4) | 53 (29.9) | 88 (48.6) | NS | NS |
| Traditional chemotherapy | 150 (41.9) | 45 (25.4) | 105 (58.0) | NS | NS |
| Targeted agent | 67 (18.7) | 18 (10.2) | 49 (27.1) | 0.33 (0.16-0.69) | .003 |
| Other immunotherapy | 19 (5.3) | 13 (7.3) | 6 (3.3) | NS | NS |
| ICI precipitating first cirAE or irAE | |||||
| Anti–PD-1/PDL-1 | 275 (76.8) | 119 (67.2) | 156 (86.2) | 1 [Reference] | |
| Anti–CTLA-4 | 14 (3.0) | 13 (7.3) | 1 (0.6) | NS | |
| Anti–PD-1/PDL-1 + CTLA-4 | 69 (19.3) | 45 (25.6) | 24 (13.3) | 2.78 (1.42-5.44) | .003 |
| Time to first cirAE, median (IQR), dc,d | 49 (19-146) | 43 (17-126) | 53 (20-166) | NS | NS |
| Morphologic characteristics of first cirAE | |||||
| Maculopapular or papulopustular, NOS | 186 (52.0) | 96 (54.2) | 90 (49.7) | 1 [Reference] | |
| Drug hypersensitivity, NOS | 17 (4.7) | 9 (5.1) | 8 (4.4) | NS | NS |
| Eczematous | 25 (7.0) | 9 (5.1) | 16 (8.8) | NS | NS |
| Lichenoid | 14 (3.9) | 5 (2.8) | 9 (5.0) | NS | NS |
| Isolated pruritus | 66 (18.4) | 32 (18.1) | 34 (18.8) | NS | NS |
| Psoriasis | 12 (3.4) | 7 (4.0) | 5 (2.8) | NS | NS |
| Vitiligo | 9 (2.5) | 7 (4.0) | 2 (1.1) | NS | NS |
| Mucositis | 9 (2.5) | 6 (3.4) | 3 (1.7) | 5.28 (1.11-24.26) | .04 |
| Othere | 20 (5.6) | 6 (3.4) | 14 (7.7) | NS | NS |
| Multiple cirAEs | 82 (22.9) | 55 (31.1) | 27 (14.9) | NS | NS |
| Peak CTCAE severity of first cirAE, median (IQR) | 1 (1-2) | 1 (1-2) | 1 (1-2) | NS | NS |
| Multiple irAEs | 67 (37.9) | NA | NA | ||
| Time to first irAE, median (IQR), d | 96 (50-190) | NA | NA | ||
| Time to all irAEs, median (IQR), d | 115 (57-229) | NA | NA | ||
Abbreviations: cirAE, cutaneous immune-related adverse event; CTCAE, Common Terminology Criteria For Adverse Events, Version 5.0; CTLA-4, cytotoxic T-lymphocyte antigen-4; ECOG, Eastern Cooperative Oncology Group; ICI, immune checkpoint inhibitor; IQR, interquartile range; irAE, noncutaneous immune-related adverse event; NA, not applicable; NOS, not otherwise specified; NS, not significant; OR, odds ratio; PD-1, programmed cell death-1; PD-L1, PD-1-ligand 1; PMR, polymyalgia rheumatica.
A P value <.05 represents a significant association between the specific patient feature and occurrence of any irAE, using the stated reference category as baseline.
Other cancer types included genitourinary (renal, urothelial), gynecologic (cervical, ovarian), breast, hematologic (Hodgkin lymphoma, non-Hodgkin lymphoma), cutaneous (nonmelanoma skin cancers, Merkel cell carcinoma), endocrine (neuroendocrine, adrenocortical, thyroid), musculoskeletal/soft tissue (sarcoma), and neurologic (meningioma, glioblastoma) cancers.
Median time to onset of initial mucositis cirAE and first irAE, when co-occurring: 21 days (IQR, 17-41 days) and 231 days (IQR, 46-424 days). Median time to onset of initial mucositis cirAE and gastrointestinal irAE (including gastroenterocolitis), when co-occurring: 21 days (IQR, 16-21 days) and 63 days (IQR, 40-388 days). Median time to onset of initial mucositis cirAE and rheumatologic irAE (including arthritis), when co-occurring: 199 days (IQR, 41-357 days) and 416 days (IQR, 407-424 days).
Median time to onset of initial psoriasiform cirAE and endocrine irAE, when co-occurring: 181 days (IQR, 108-323 days) and 180 days (IQR, 154-181 days). Median time to onset of initial psoriasiform cirAE and thyroiditis irAE, when co-occurring: 252 days (IQR, 94-399 days) and 167 days (IQR, 150-180 days).
Other morphologic characteristics of first cirAE included bullous pemphigoid (overall number of patients, 7; with irAE, 0; without irAE, 7), urticarial reaction (overall, 4; with irAE, 1; without irAE, 3), erythema multiformelike reaction (overall, 4; with irAE, 3; without irAE, 1), panniculitis (overall, 2; with irAE, 1; without irAE, 1), Stevens-Johnson syndromelike reaction (overall, 1; with irAE, 0; without irAE, 1), Sweet syndrome (overall, 1; with irAE, 0; without irAE, 1), and dyshidrotic eczema (overall, 1; with irAE, 1; without irAE, 0).