Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab

Abstract

Ipilimumab was the first immunotherapy approved for metastatic melanoma in decades and is currently registered as a second-line treatment. However, new immunotherapies, in combination with ipilimumab, offer even better clinical outcomes for patients compared with single-agent treatments, at the expense of improved toxicity. The aim of this study was to evaluate the feasibility of ipilimumab outside the clinical trials and to identify survival predictors for treatment benefit. Data were collected on 47 advanced melanoma patients treated with ipilimumab between 2010 and 2015 at a single center. Association of clinical characteristics (including primary tumor characteristics), serum lactate dehydrogenase (LDH), erythrocyte sedimentation rate, absolute eosinophil, lymphocyte, and neutrophil count, neutrophil/lymphocyte and eosinophil/lymphocyte ratio with toxicity and clinical outcome were assessed using univariate and multivariate analysis. Median progression-free survival at a median follow-up of 10 months was 2.7 months and median overall survival was 9.8 months. Objective response was observed in 17% of patients and the disease control rate at week 24 was 40%. The 1- and 2-year survival rates documented were 40 and 28%, respectively. Significant association between high LDH level (>1.5× upper limit of normal) and decreased overall survival was demonstrated in uni- and multivariate analysis (hazard ratio [HR]: 3.554, 95% CI: 1.225-10.306, p = 0.019). Neither biomarkers nor clinical outcome were associated with toxicity. Using baseline serum LDH to identify patients most likely to benefit from ipilimumab therapy could serve as a simple and inexpensive biomarker of clinical outcome.

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

“…In addition to clinical features, peripheral immune cells and inflammatory factors have also been recently explored as possible biomarkers of response to ICIs in melanoma, lung cancer and other types of tumors treated with ICIs [12,[39][40][41][42][43][44][45].…”

Blood eosinophilic relative count is prognostic for breast cancer and associated with the presence of tumor at diagnosis and at time of relapse

“…13,14 The role of peripheral eosinophil count has been studied mainly in melanoma and in lung cancer patients treated with immunotherapy. [15][16][17][18][19][20][21][22][23][24][25] Concerning breast cancer, less studies have been published so far and their role is still controversial. A first study, published in 1983, showed that high baseline eosinophil count was associated with a lower recurrence rate in 419 breast cancer patients.…”

Prognostic and predictive factors associated with ipilimumab-related adverse events: a retrospective analysis of 11 NCI-sponsored phase I clinical trials

“…In a retrospective analysis of 183 patients treated with ipilimumab, LDH and neutrophil-to-lymphocyte ratio could differentiate patients into high, moderate and low risk of death, but was not associated with toxicity [12]. Another analysis conducted on 47 advanced melanoma patients also demonstrated a significant association between higher LDH and poor prognosis, but no association between LDH and toxicity [20].…”