Abstract Preexisting atopy, particularly allergic rhinitis, is consistently associated with decreased risk of glioma, and there is evidence that preexisting autoimmune conditions may also decrease risk. Glioblastoma is both locally and systemically immunosuppressive and, unlike many other forms of cancer, its initiation is not strongly linked with chronic inflammation. Therefore, history of immune hypersensitivity could be associated with improved anti-glioma immunosurveillance. We leveraged Surveillance, Epidemiology and End Results (SEER) data combined with Medicare claims to investigate the effect of preexisting immune hypersensitivities on overall survival of glioblastoma patients receiving resection, radiation, and temozolomide (standard of care, or SOC) from 2008-2019. Patients <66 years of age, enrolled in Medicare Advantage, not continuously enrolled in Medicare Part A/B, missing follow-up, reported by autopsy/death certificate only, or who did not receive surgery were excluded. Prior history of immune hypersensitivity (≥6 months prior to primary cancer diagnosis) was identified by ICD-9/ICD-10 codes. Treatment pattern was determined using ICD-9/ICD-10 and HCPCS/CPT codes. Conditions were classified into broad immune hypersensitivity types: type I (IgE-mediated, including atopy), type II (IgG- or IgM-mediated), type III (immune complex-mediated, including lupus and rheumatoid arthritis), and type IV (cell-mediated). Survival comparisons were made using Cox proportional hazard models adjusted for demographics, extent of resection, and Charlson comorbidity score (excluding immune conditions) to estimate hazard ratios, 95% confidence intervals, and p-values. Overall, 44% of 3,426 glioblastoma patients who received SOC had an immune hypersensitivity (type I: 33%, type II: 4%, type III: 8%, and type IV: 15%). These conditions were significantly more common in females (47% vs 41%, p<0.001). After adjustment, only type III immune sensitivity was associated with improved OS (HR=0.81, 95% CI:0.71-0.92, p=0.002). These results suggest that underlying immune-complex mediated hypersensitivity may improve treatment response and prognosis in glioblastoma, and that these pathways could potentially be exploited for therapy.
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