Decreased relative lymphocyte count in peripheral blood might reflect severe immune-related adverse events in melanoma patients treated with nivolumab
Yasuhiro Fujisawa1, Koji Yoshino2, Hiroo Hata3, Taku Fujimura4, Takeru Funakoshi5, Atsushi Otsuka6, Shigeto Matsushita7, Yuki Yamamoto8
1Department of Dermatology, University of Tsukuba; 2Department of Dermatology, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital; 3Department of Dermatology, Hokkaido University; 4Department of Dermatology, Tohoku University; 5Department of Dermatology, Keio University; 6Department of Dermatology, Kyoto University; 7Department of Dermato-Oncology/Dermatology, National Hospital Organization Kagoshima Medical Center; 8Department of Dermatology, Wakayama Medical University
Background: Although nivolumab significantly prolongs survival in patients with metastatic melanoma, about 10% of patients who receive nivolumab monotherapy experience severe, even fatal immune-related adverse events (irAEs). Therefore, biomarkers that can predict adverse events are of great interest. We aimed to identify changes in routine blood count parameters associated with the occurrence of serious irAEs such as grade 3/4 (G3/4) or lung/gastrointestinal (lung/GI) irAEs in melanoma patients treated with nivolumab.
Materials and methods: We retrospectively collected clinical data of 101 melanoma patient treated with nivolumab from 8 institutes in Japan. Association between severe irAEs and fluctuation of routine blood count parameters (total white blood cell count, relative neutrophil, monocyte, lymphocyte and eosinophil count) during the treatment was investigated using logistic regression analyses. Receiver-operator curve was used to determine a cutoff value of the blood count parameters and area under the curve (AUC).
Results: G3/4 irAEs were associated with increased total white blood cell count (WBC, odds ratio=1.02, P=0.034, cutoff value=+27%, AUC=0.68) and decreased relative lymphocyte count (rLym, odds ratio=0.98, P=0.042, cutoff value=-23%, AUC=0.65) only by univariate analysis. On the other hand, multivariate analysis showed that same factors; increased WBC (odds ratio=1.03, P=0.014, cutoff value=+59.1%, AUC=0.79) and decreased rLym (odds ratio=0.95, P=0.012, cutoff value=-32.3%, AUC=0.81) were independent factors associated with lung/GI irAEs.
Conclusions: These results suggested that increased WBC and decreased rLym were associated with G3/4 and lung/GI irAEs. Although our analysis was based on the data point when we noticed the occurrence of irAEs and not predictive, we can use these factors as the “signal” of severe irAE occurrence.