Association Between Immune-Related Adverse Events and Clinical Efficacy in Patients with Melanoma Treated With Nivolumab: A Multicenter Retrospective Study

Naoto Okada, Hitoshi Kawazoe, Kenshi Takechi, Yoshihiro Matsudate, Ryo Utsunomiya, Yoshito Zamami, Mitsuhiro Goda, Masaki Imanishi, Masayuki Chuma, Noriaki Hidaka, Koji Sayama, Yoshiaki Kubo, Akihiro Tanaka, Keisuke Ishizawa

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose: Nivolumab, an anti–programmed death 1 antibody, produces antitumor effects by activating host immunity, which also causes immune-related adverse events (irAEs). The aim of this study was to analyze the association between antitumor effect and irAEs induced by nivolumab in patients with melanoma. Methods: Fifteen patients with melanoma who had received nivolumab at Tokushima University Hospital or Ehime University Hospital between January 2015 and December 2016 were enrolled in this study. Patients who had and did not have irAEs during nivolumab treatment were classified into an irAEs-positive group (n = 8) and an irAEs-negative group (n = 7), respectively. We compared the disease control rate (DCR) and overall survival (OS) between the 2 groups. Data on blood cell counts were also analyzed. Findings: After a median of 4 cycles of nivolumab treatment, irAEs occurred. The DCRs were 75% and 14% in the irAEs-positive and irAEs-negative groups, respectively (p < 0.05). OS in the irAEs-positive group was higher than that in the irAEs-negative group (p < 0.05). Multivariable Cox proportional hazards regression analysis revealed that irAE occurrence affected OS with nivolumab treatment. Moreover, the increase in baseline peripheral lymphocyte count at the time of onset of irAEs was significantly greater in the irAEs-positive group than in the irAEs-negative group after 4 cycles of nivolumab treatment (p < 0.05). Implications: Our study indicated that clinical response with nivolumab treatment improves with irAE occurrence in patients with melanoma. Moreover, the early increase in peripheral lymphocyte count may act as a biomarker for predicting the occurrence of irAEs induced by nivolumab.

Original languageEnglish
JournalClinical Therapeutics
DOIs
Publication statusAccepted/In press - 2018 Jan 1
Externally publishedYes

Fingerprint

Multicenter Studies
Melanoma
Retrospective Studies
Lymphocyte Count
Therapeutics
nivolumab
Survival
Blood Cell Count
Immunity
Survival Rate
Biomarkers
Regression Analysis
Antibodies

Keywords

  • Biomarker
  • Immune-related adverse event
  • Melanoma
  • Nivolumab
  • Overall response rate

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Association Between Immune-Related Adverse Events and Clinical Efficacy in Patients with Melanoma Treated With Nivolumab : A Multicenter Retrospective Study. / Okada, Naoto; Kawazoe, Hitoshi; Takechi, Kenshi; Matsudate, Yoshihiro; Utsunomiya, Ryo; Zamami, Yoshito; Goda, Mitsuhiro; Imanishi, Masaki; Chuma, Masayuki; Hidaka, Noriaki; Sayama, Koji; Kubo, Yoshiaki; Tanaka, Akihiro; Ishizawa, Keisuke.

In: Clinical Therapeutics, 01.01.2018.

Research output: Contribution to journalArticle

Okada, N, Kawazoe, H, Takechi, K, Matsudate, Y, Utsunomiya, R, Zamami, Y, Goda, M, Imanishi, M, Chuma, M, Hidaka, N, Sayama, K, Kubo, Y, Tanaka, A & Ishizawa, K 2018, 'Association Between Immune-Related Adverse Events and Clinical Efficacy in Patients with Melanoma Treated With Nivolumab: A Multicenter Retrospective Study', Clinical Therapeutics. https://doi.org/10.1016/j.clinthera.2018.11.004
Okada, Naoto ; Kawazoe, Hitoshi ; Takechi, Kenshi ; Matsudate, Yoshihiro ; Utsunomiya, Ryo ; Zamami, Yoshito ; Goda, Mitsuhiro ; Imanishi, Masaki ; Chuma, Masayuki ; Hidaka, Noriaki ; Sayama, Koji ; Kubo, Yoshiaki ; Tanaka, Akihiro ; Ishizawa, Keisuke. / Association Between Immune-Related Adverse Events and Clinical Efficacy in Patients with Melanoma Treated With Nivolumab : A Multicenter Retrospective Study. In: Clinical Therapeutics. 2018.
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T2 - A Multicenter Retrospective Study

AU - Okada, Naoto

AU - Kawazoe, Hitoshi

AU - Takechi, Kenshi

AU - Matsudate, Yoshihiro

AU - Utsunomiya, Ryo

AU - Zamami, Yoshito

AU - Goda, Mitsuhiro

AU - Imanishi, Masaki

AU - Chuma, Masayuki

AU - Hidaka, Noriaki

AU - Sayama, Koji

AU - Kubo, Yoshiaki

AU - Tanaka, Akihiro

AU - Ishizawa, Keisuke

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N2 - Purpose: Nivolumab, an anti–programmed death 1 antibody, produces antitumor effects by activating host immunity, which also causes immune-related adverse events (irAEs). The aim of this study was to analyze the association between antitumor effect and irAEs induced by nivolumab in patients with melanoma. Methods: Fifteen patients with melanoma who had received nivolumab at Tokushima University Hospital or Ehime University Hospital between January 2015 and December 2016 were enrolled in this study. Patients who had and did not have irAEs during nivolumab treatment were classified into an irAEs-positive group (n = 8) and an irAEs-negative group (n = 7), respectively. We compared the disease control rate (DCR) and overall survival (OS) between the 2 groups. Data on blood cell counts were also analyzed. Findings: After a median of 4 cycles of nivolumab treatment, irAEs occurred. The DCRs were 75% and 14% in the irAEs-positive and irAEs-negative groups, respectively (p < 0.05). OS in the irAEs-positive group was higher than that in the irAEs-negative group (p < 0.05). Multivariable Cox proportional hazards regression analysis revealed that irAE occurrence affected OS with nivolumab treatment. Moreover, the increase in baseline peripheral lymphocyte count at the time of onset of irAEs was significantly greater in the irAEs-positive group than in the irAEs-negative group after 4 cycles of nivolumab treatment (p < 0.05). Implications: Our study indicated that clinical response with nivolumab treatment improves with irAE occurrence in patients with melanoma. Moreover, the early increase in peripheral lymphocyte count may act as a biomarker for predicting the occurrence of irAEs induced by nivolumab.

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KW - Nivolumab

KW - Overall response rate

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