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Abstract
Background Immune checkpoint inhibitors (ICI) have a high frequency of any-grade immune-related adverse events (irAEs) that can involve multiple organs. Similar to EGFR inhibitors, dermatological adverse events may be predictive of efficacy. Additional data is needed to guide the decision to continue, defer, or switch therapy when these irAEs occur.
Methods We created an IRB-approved retrospective registry of all patients who received at least one dose of an ICI for any indication between 2/1/2011 and 4/7/2022 at a comprehensive cancer center and its outreach clinics. Study personnel reviewed the electronic medical record, captured all treatment-emergent adverse events that were in routine clinical documentation, and estimated attribution and severity using the Common Terminology Criteria for Adverse Events. Case report forms were stored in REDCap and validated with data quality rules; research specialists at Vasta Global captured most clinical outcomes. Time variables were censored at the date of last follow-up. A multivariable Cox proportional hazards model was built. The proportional hazards assumption was validated graphically. SAS v9.4 was used for all analyses.
Results The final cohort included 3141 patients, of which 1176 (37.4%) experienced at least one irAE. 267 (8.5%) of all patients experienced a dermatological irAE; and among them, 153 (57.3%) also experienced a second, non-dermatological irAE. Melanoma and renal cell carcinoma were the two most likely primary tumors to experience dermatological plus second irAE with 12.1% and 10.2% respectively compared to the incidence of 3.8% among all other tumor primaries (p<0.01; p<0.01). Among patients with dermatological plus a second irAE, the first events occurred sooner (median 1.4 months) than either separately (median 2.1 and 2.1 months respectively). When modeled to control for age, tumor primary, and stage, the patients with dermatological plus a second irAE conferred the highest survival benefit compared to no event (HR 0.27; 95% CI 0.20–0.28) (figure 1).
Conclusions In this study, the pattern of irAEs were shown to be meaningful in the context of survival. Over half of patients with dermatological irAEs experienced another system irAE. These patients experienced a shorter time to the first event and a more prolonged overall survival than the other study groups, suggesting a robust response. Further studies should investigate this sub-population to identify a potential genomic or biomarker indicator for hyper-responsiveness to immunotherapy.
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