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

Yasuhiro Fujisawa, Koji Yoshino, Atsushi Otsuka, Takeru Funakoshi, Taku Fujimura, Yuki Yamamoto, Hiroo Hata, Masahiko Gosho, Ryota Tanaka, Kei Yamaguchi, Yumi Nonomura, Ikuko Hirai, Sadanori Furudate, Hisako Okuhira, Keisuke Imafuku, Megumi Aoki, Shigeto Matsushita

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)225-231
Number of pages7
JournalJournal of Dermatological Science
Issue number2
Publication statusPublished - 2017 Nov


  • Adverse event
  • Blood cell parameters
  • Checkpoint inhibitor
  • Melanoma
  • Relative lymphocyte count
  • White blood cell count


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