Atopy improves survival and decreases risk of brain metastasis in cutaneous melanoma
Authors: Neff Corey , Price Mackenzie , Cioffi Gino , Liu Zhen , Walsh Rabina , Barnholtz-Sloan Jill S. , Walsh Kyle M. , Salama April K. S. , Anders Carey K. , Fecci Peter E. , Ostrom Quinn T. 
Published: May 2024

ABSTRACTImportanceDevelopment of new therapies in melanoma has increased survival, and as a result more patients are living to develop brain metastasis (BrM). Identifying patients at increased risk of BrM is therefore of significant public health importance.ObjectiveTo determine whether history of atopy is associated with improved survival or reduced incidence of BrM in cutaneous melanoma.DesignA retrospective cohort study conducted from June 2022 to March 2024.SettingPopulation-based in states with Surveillance, Epidemiology and End Results (SEER) supported cancer registries.ParticipantsIndividuals (≥65 years) diagnosed with cutaneous melanoma between January 1, 2008 and December 31, 2017 that are participants in traditional Medicare.Exposure(s)Individuals were compared that had history of atopy (allergic rhinitis, atopic dermatitis, asthma, and/or allergic/atopic conjunctivitis) diagnosed prior to melanoma diagnosis, ascertained using ICD-9 or ICD-10 codes in Medicare claims.Main Outcome(s) and Measure(s)Primary endpoints were diagnosis with a BrM or death during the follow-up period. Associations between atopy and endpoints were assessed using cox proportional hazards models to estimate hazard ratios (HR) and p-values.ResultsA total of 29,956 cutaneous melanoma cases were identified (median age 76, 60% male and 97% non-Hispanic White). Overall, 7.1% developed BrM during follow up. Among the 35% that had history of atopy, the most common condition was atopic dermatitis (19%). After adjustment for demographic and prognostic factors, atopy was associated with a 16% decrease in death (HR=0.84 [95%CI:0.80-0.87], pFDR<0.001). Among those with non-metastatic disease at time of diagnosis, atopy conferred a 15% decrease in cumulative incidence BrM (HR=0.85 [95%CI: 0.76-0.94], pFDR=0.006), with a 25% decrease associated with atopic dermatitis (HR=0.75 [95%CI:0.65-0.86], pFDR<0.001). Among those with metastatic disease at diagnosis (any metastatic site), only those who received immune checkpoint inhibitors had a survival benefit associated with atopy (HR=0.31, [95%CI:0.15-0.64], p=0.001 vs HR=1.41, [95%CI:0.87-2.27], p=0.165).Conclusions and RelevanceAtopy, particularly atopic dermatitis, was significantly associated with improved survival and decreased incidence of BrM. The improved survival associated with these conditions in the context of immunotherapy suggests that these conditions in the elderly may identify those with more robust immune function that may be more responsive to treatment.Key PointsQuestion:Does atopy affect outcomes in cutaneous melanoma?Findings:In a retrospective cohort study, elderly individuals with prior diagnosis of atopy had significant improved overall survival and decreased incidence of brain metastasis as compared to individuals without atopy.Meaning:History of atopy may identify a subgroup within melanoma cases that has improved response to treatment and a more robust immune system which decreases risk of metastasis to the brain.