Naoto Okada1, Hitoshi Kawazoe2, Kenshi Takechi3, Yoshihiro Matsudate4, Ryo Utsunomiya5, Yoshito Zamami6, Mitsuhiro Goda7, Masaki Imanishi7, Masayuki Chuma3, Noriaki Hidaka2, Koji Sayama5, Yoshiaki Kubo4, Akihiro Tanaka2, Keisuke Ishizawa8. 1. Department of Pharmacy, Tokushima University Hospital, Kuramoto, Tokushima, Japan. Electronic address: naoto-o@tokushima-u.ac.jp. 2. Division of Pharmacy, Ehime University Hospital, Shitsukawa, Toon, Ehime, Japan. 3. Clinical Trial Center for Developmental Therapeutics, Tokushima University Hospital, Kuramoto, Tokushima, Japan. 4. Department of Dermatology, Tokushima University Graduate School of Medical Science, Kuramoto, Tokushima, Japan. 5. Department of Dermatology, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime, Japan. 6. Department of Pharmacy, Tokushima University Hospital, Kuramoto, Tokushima, Japan; Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences, Kuramoto, Tokushima, Japan. 7. Department of Pharmacy, Tokushima University Hospital, Kuramoto, Tokushima, Japan. 8. Department of Pharmacy, Tokushima University Hospital, Kuramoto, Tokushima, Japan; Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences, Kuramoto, Tokushima, Japan. Electronic address: ishizawa@tokushima-u.ac.jp.
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.
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.
Authors: Satya Das; Kristen K Ciombor; Sigurdis Haraldsdottir; Yoanna Pumpalova; Ibrahim H Sahin; G Pineda; Yu Shyr; E P Lin; Chih-Yuan Hsu; Shih-Kai Chu; Laura W Goff; Dana B Cardin; Mehmet A Bilen; George A Fisher; Christina Wu; Jordan Berlin Journal: Oncologist Date: 2020-01-14
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Authors: Saby George; Elizabeth J Bell; Ying Zheng; Ruth Kim; John White; Geeta Devgan; Jodi Smith; Lincy S Lal; Nicole M Engel-Nitz; Frank X Liu Journal: Oncologist Date: 2021-05-29