Fluctuations in routine blood count might signal severe immune-related adverse events in melanoma patients treated with nivolumab

Background: Although nivolumab significantly prolongs survival of metastatic melanoma, about 10% of patients experience severe, even fatal immune-related adverse events (irAEs). Biomarkers to predict irAEs are, therefore, of great interest. Objective: We aimed to correlate changes in routine blood count parameters to the occurrence of serious irAEs (grade 3/4 [G3/4] or lung/gastrointestinal [lung/GI] irAEs) in patients with melanoma who were treated with nivolumab. Methods: We retrospectively analyzed data from 101 patient with melanoma treated with nivolumab from 8 institutes in Japan. We used logistic regression analyses to investigate associations between severe irAEs and fluctuations in routine blood count parameters (total white blood cell [WBC] count, relative neutrophil, monocyte, lymphocyte, and eosinophil count) during the treatment. Receiver operating characteristic curve was used to determine a cutoff value for the blood count parameters and area under the curve (AUC). Results: Univariate analysis revealed that G3/4 irAEs were associated with increased total WBC count (P = 0.034, cutoff value = +27%, AUC= 0.68, odds ratio [OR] = 1.58) and decreased relative lymphocyte count (RLC, P= 0.042, cutoff value = -23%, AUC= 0.65, OR= 1.65). However, multivariate analysis showed that the same factors, increased WBC count (P = 0.014, cutoff value = +59.1%, AUC = 0.79, OR= 6.04) and decreased RLC (P = 0.012, cutoff value = 32.3%, AUC= 0.81, OR= 5.01) were independent factors associated with lung/GI irAEs. Conclusions: Our results suggest that increased WBC count and decreased RLC are associated with G3/4 and lung/GI irAEs. Our analysis was based on the data point at which irAE occurrence was noticed and, therefore, these factors are not predictive, however, they could be a "signal" of severe irAE occurrence in patients with melanoma treated with nivolumab. (C) 2017 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.