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 journalArticle

10 Citations (Scopus)

Abstract

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
JournalJournal of Dermatological Science
DOIs
Publication statusAccepted/In press - 2017

Fingerprint

Area Under Curve
Melanoma
Blood
Leukocyte Count
Odds Ratio
Lymphocyte Count
Lung
Lymphocytes
Eosinophils
ROC Curve
Monocytes
Japan
Neutrophils
Multivariate Analysis
Biomarkers
Logistic Models
Regression Analysis
nivolumab
Logistics
Survival

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

Fluctuations in routine blood count might signal severe immune-related adverse events in melanoma patients treated with nivolumab. / Fujisawa, Yasuhiro; Yoshino, Koji; Otsuka, Atsushi; Funakoshi, Takeru; Fujimura, Taku; Yamamoto, Yuki; Hata, Hiroo; Gosho, Masahiko; Tanaka, Ryota; Yamaguchi, Kei; Nonomura, Yumi; Hirai, Ikuko; Furudate, Sadanori; Okuhira, Hisako; Imafuku, Keisuke; Aoki, Megumi; Matsushita, Shigeto.

In: Journal of Dermatological Science, 2017.

Research output: Contribution to journalArticle

Fujisawa, Y, Yoshino, K, Otsuka, A, Funakoshi, T, Fujimura, T, Yamamoto, Y, Hata, H, Gosho, M, Tanaka, R, Yamaguchi, K, Nonomura, Y, Hirai, I, Furudate, S, Okuhira, H, Imafuku, K, Aoki, M & Matsushita, S 2017, 'Fluctuations in routine blood count might signal severe immune-related adverse events in melanoma patients treated with nivolumab', Journal of Dermatological Science. https://doi.org/10.1016/j.jdermsci.2017.07.007
Fujisawa, Yasuhiro ; Yoshino, Koji ; Otsuka, Atsushi ; Funakoshi, Takeru ; Fujimura, Taku ; Yamamoto, Yuki ; Hata, Hiroo ; Gosho, Masahiko ; Tanaka, Ryota ; Yamaguchi, Kei ; Nonomura, Yumi ; Hirai, Ikuko ; Furudate, Sadanori ; Okuhira, Hisako ; Imafuku, Keisuke ; Aoki, Megumi ; Matsushita, Shigeto. / Fluctuations in routine blood count might signal severe immune-related adverse events in melanoma patients treated with nivolumab. In: Journal of Dermatological Science. 2017.
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abstract = "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.",
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author = "Yasuhiro Fujisawa and Koji Yoshino and Atsushi Otsuka and Takeru Funakoshi and Taku Fujimura and Yuki Yamamoto and Hiroo Hata and Masahiko Gosho and Ryota Tanaka and Kei Yamaguchi and Yumi Nonomura and Ikuko Hirai and Sadanori Furudate and Hisako Okuhira and Keisuke Imafuku and Megumi Aoki and Shigeto Matsushita",
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TY - JOUR

T1 - Fluctuations in routine blood count might signal severe immune-related adverse events in melanoma patients treated with nivolumab

AU - Fujisawa, Yasuhiro

AU - Yoshino, Koji

AU - Otsuka, Atsushi

AU - Funakoshi, Takeru

AU - Fujimura, Taku

AU - Yamamoto, Yuki

AU - Hata, Hiroo

AU - Gosho, Masahiko

AU - Tanaka, Ryota

AU - Yamaguchi, Kei

AU - Nonomura, Yumi

AU - Hirai, Ikuko

AU - Furudate, Sadanori

AU - Okuhira, Hisako

AU - Imafuku, Keisuke

AU - Aoki, Megumi

AU - Matsushita, Shigeto

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Adverse event

KW - Blood cell parameters

KW - Checkpoint inhibitor

KW - Melanoma

KW - Relative lymphocyte count

KW - White blood cell count

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U2 - 10.1016/j.jdermsci.2017.07.007

DO - 10.1016/j.jdermsci.2017.07.007

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