Abstract
Recently antibiotic exposure has been associated with worse outcomes in patients undergoing treatment with antibodies directed against programmed cell death protein-1 (PD-1). We reviewed data of 1264 patients enrolled at Melanoma Skin and Ocular Tissue Repositories at University of Iowa Hospitals and Clinic. Reviewed data included patient demographics, prior medical history, baseline hematologic and disease parameters and outcomes including progression-free survival (PFS) and overall survival (OS). Cox regression models were used to determine predictive markers. Overall, 169 patients with advanced cutaneous melanoma received anti-PD-1 based therapies. Median follow up was 18.46 (range 0.89 to 62.52) months. On multivariable analysis brain metastasis, higher absolute neutrophil count (ANC) and lower absolute lymphocyte count were associated with poorer PFS while brain and liver metastasis and lower albumin were associated with poorer OS. Prior antibiotics, radiation as well as age, gender, basal metabolic index (BMI), smoking status, BRAF mutation, line of therapy (first or latter), prior treatments (ipilimumab or BRAF inhibitors), hemoglobin, neutrophil-to-lymphocyte ratio, white blood cell, platelet and eosinophil counts were not associated with PFS or OS in multivariable analysis. Contrary to some prior studies BMI, radiation, and antibiotics were not associated with PFS or OS.
Highlights
Management of metastatic melanoma has undergone a tectonic shift with the advent of immunotherapies and targeted therapies
Our study presents a detailed analysis of various baseline variables which are part of standard of care to determine clinical predictors to anti-PD-1 therapies
Metastasis to the brain was associated with worse progression-free survival (PFS) and overall survival (OS)
Summary
Management of metastatic melanoma has undergone a tectonic shift with the advent of immunotherapies and targeted therapies. Since 2011, 10 agents have been approved for the treatment of metastatic melanoma including two programmed cell death protein-1 (PD-1) antibodies, pembrolizumab and nivolumab, which are approved for treatment of metastatic melanoma as front-line therapy [1]. These agents have significantly improved the historical median overall survival (OS) of patients with metastatic melanoma from 6.2 months [2] to more than 3 years [3]. Though anti-PD-1 therapies have been approved for all patients with metastatic melanoma regardless of PD-L1 expression, it is not known which patients will derive benefit from them. A great deal of effort is being made to identify predictive biomarkers including evaluation of PD-L1 expression, tumor infiltrating lymphocytes, tumor mutational burden, microsatellite instability, mismatch-repair deficiency, neoantigen load, gene expression signatures, T-cell receptor diversity, and clonality, circulating immune-cell subsets, serum protein signatures, soluble PD-L1, gut microbiome, human leukocyte antigen genotype, and germline single-nucleotide polymorphism [4]
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