Revisiting the Association Between Skin Toxicity and Better Response in Melanoma Patients Treated With Immune Checkpoint Inhibitors
Nicholas Gulati, MD, PhD, NYU Grossman School of Medicine, New York, New York
Disclosures: None.
Immune checkpoint inhibition (ICI) improves survival outcomes for patients with metastatic melanoma, but serious immune-related adverse events requiring intervention with immunosuppressive medications occur in a subset of patients. Skin toxicity (ST) has been reported to be associated with better response to ICI. However, understudied factors, such as ST severity and potential survivor bias, may influence the strength of these observed associations. To examine the potential confounding impact of such variables, we analyzed metastatic melanoma patients enrolled prospectively in a clinicopathological database with protocol-driven follow-up and treated with ICI. We tested the associations between developing ST, stratified as none (n=257), mild (n=86), and severe (n=44), and progression-free survival (PFS) and overall survival in univariable and multivariable analyses. We defined severe ST as a skin event that required treatment with systemic corticosteroids. To account for the possibility of longer survival leading to adverse events instead of the reverse, we treated ST as a time-dependent covariate in an adjusted model. Mild ST was significantly associated with improved PFS and overall survival (P=.001 and P=.018, respectively) in univariable analysis and with improved PFS in multivariable analysis (P=.020). However, these associations lost significance after adjusting for the time from treatment initiation to time of skin event (P>.05). Severe ST was not associated with improved outcomes. Our data reveal the influence of event severity and time to event as covariates in analyzing the relationship between ST and ICI outcomes. Further, we reinforce the importance of identifying baseline predictors of response and toxicity to ICI to optimize treatment selection and prophylactic care when indicated.
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