Investigating the impact of medical comorbidities in patients taking beta blockers and treated with immunotherapy for metastatic melanoma.

Abstract

e15162 Background: Combined administration of β-adrenergic antagonist with IL-2, anti-PD-1, and/or anti-CTLA-4 immunotherapy was associated with a better overall survival in metastatic melanoma patients. This result was also reinforced by the significant reduction in tumor growth in a murine melanoma model when a β2-selective antagonist was combined with anti-PD1/IL-2 immunotherapy. Here we sought to elucidate the impact of the various comorbidities behind the indications of β-blockers, and how they might have influenced the patients’ immunotherapy treatment response. Methods: A single-institution retrospective chart review was performed to examine the medical comorbidities with indications for β-blockers in the melanoma patients who received IL-2, αPD-1 and/or αCTLA-4 immunotherapy between January 2000 and March 2015. Two groups were identified: one that took a selective β-1 blocker (N = 41), and another that took a nonselective pan β-blocker (N = 17). The primary analysis compared the distribution of different comorbidity types between two groups, using the Fisher’s exact test. A secondary analysis examined the association of overall survival and the β-blocker groups by further controlling for comorbid conditions, using the multivariate Cox Proportional-Hazard regression model. Results: Seven different comorbidities with indications for β-blocker usage were identified. Of those comorbidities, only the presence of ischemic heart disease was marginally different between the two groups (β-1 group 19.5% vs. pan-β group 47.1%, p-value = 0.0697). There was no difference for overall survival between each of the comorbidity conditions. When performing the multivariate Cox Proportional-Hazard regression model, β-blocker usage still remained statistically significant for the overall survival (HR 0.27, CI 0.0966-0.768, p = 0.0139), even after controlling for the comorbid conditions. Conclusions: Immunotherapy with pan β-adrenergic blockade was associated with a significantly improved overall survival rate for metastatic melanoma. Furthermore, having a comorbid condition that indicated for the prescription of β-blockers was not a factor in establishing this survival rate.