Investigation of clinical factors associated with longer overall survival in advanced melanoma patients treated with sequential ipilimumab

Yusuke Muto, Shigehisa Kitano, Arata Tsutsumida, Kenjiro Namikawa, Akira Takahashi, Yoshio Nakamura, Takeharu Yamanaka, Noboru Yamamoto, Naoya Yamazaki

Research output: Contribution to journalArticle

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Abstract

Melanoma is one of the most serious form of skin cancer. Nowadays, ipilimumab is used for advanced melanoma refractory to first-line anti-programmed death 1 (PD-1) antibodies. Thirty patients (male : female ratio, 18:12; median age, 60.5 years) sequentially treated with ipilimumab after anti-PD-1 antibody (nivolumab or pembrolizumab), while 58 (male : female ratio, 27:31; median age, 66.5 years) with anti-PD-1 antibody only. The kind of therapy and schedules were as follows: nivolumab, 2 mg/kg at 3-week intervals or at 3 mg/kg every 2 week; pembrolizumab, 2 mg/kg every 3 weeks; ipilimumab, 3 mg/kg at 3-week intervals for four doses. The sequential therapy was selected for the patients with disease progression and/or recovered from severe (immune-related [ir]) adverse events (AE) after PD-1 blockade monotherapy. We evaluated multiple parameters and analyzed their relevance to overall survival (OS). The best objective response rate was 6.7% in sequential ipilimumab treatment. Median OS was 163 days (range, 16–489). Baseline absolute lymphocyte count (ALC) and performance status (PS) before sequential ipilimumab were associated with OS in univariate analyses. Baseline PS and irAE within 6 weeks after ipilimumab administration showed significant differences on multivariate analysis. Prior to first-line PD-1 blockade, these parameters were not associated with OS. The other factors (i.e. age, sex, number of doses, absolute neutrophil counts, neutrophil : lymphocyte ratio, lactate dehydrogenase and C-reactive protein) were not related to OS. Ipilimumab as sequential therapy did not appear to improve OS and was associated with more severe irAE than PD-1 blockade monotherapy. We need to carefully consider treating patients with poor PS and low ALC.

Original languageEnglish
JournalJournal of Dermatology
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Melanoma
Survival
Lymphocyte Count
Antibodies
Neutrophils
Age Factors
Skin Neoplasms
Therapeutics
ipilimumab
C-Reactive Protein
Disease Progression
Appointments and Schedules
Multivariate Analysis

Keywords

  • absolute lymphocyte count
  • anti-programmed death 1 antibody
  • ipilimumab
  • performance status
  • sequential therapy

ASJC Scopus subject areas

  • Dermatology

Cite this

Investigation of clinical factors associated with longer overall survival in advanced melanoma patients treated with sequential ipilimumab. / Muto, Yusuke; Kitano, Shigehisa; Tsutsumida, Arata; Namikawa, Kenjiro; Takahashi, Akira; Nakamura, Yoshio; Yamanaka, Takeharu; Yamamoto, Noboru; Yamazaki, Naoya.

In: Journal of Dermatology, 01.01.2019.

Research output: Contribution to journalArticle

Muto, Yusuke ; Kitano, Shigehisa ; Tsutsumida, Arata ; Namikawa, Kenjiro ; Takahashi, Akira ; Nakamura, Yoshio ; Yamanaka, Takeharu ; Yamamoto, Noboru ; Yamazaki, Naoya. / Investigation of clinical factors associated with longer overall survival in advanced melanoma patients treated with sequential ipilimumab. In: Journal of Dermatology. 2019.
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AU - Takahashi, Akira

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AB - Melanoma is one of the most serious form of skin cancer. Nowadays, ipilimumab is used for advanced melanoma refractory to first-line anti-programmed death 1 (PD-1) antibodies. Thirty patients (male : female ratio, 18:12; median age, 60.5 years) sequentially treated with ipilimumab after anti-PD-1 antibody (nivolumab or pembrolizumab), while 58 (male : female ratio, 27:31; median age, 66.5 years) with anti-PD-1 antibody only. The kind of therapy and schedules were as follows: nivolumab, 2 mg/kg at 3-week intervals or at 3 mg/kg every 2 week; pembrolizumab, 2 mg/kg every 3 weeks; ipilimumab, 3 mg/kg at 3-week intervals for four doses. The sequential therapy was selected for the patients with disease progression and/or recovered from severe (immune-related [ir]) adverse events (AE) after PD-1 blockade monotherapy. We evaluated multiple parameters and analyzed their relevance to overall survival (OS). The best objective response rate was 6.7% in sequential ipilimumab treatment. Median OS was 163 days (range, 16–489). Baseline absolute lymphocyte count (ALC) and performance status (PS) before sequential ipilimumab were associated with OS in univariate analyses. Baseline PS and irAE within 6 weeks after ipilimumab administration showed significant differences on multivariate analysis. Prior to first-line PD-1 blockade, these parameters were not associated with OS. The other factors (i.e. age, sex, number of doses, absolute neutrophil counts, neutrophil : lymphocyte ratio, lactate dehydrogenase and C-reactive protein) were not related to OS. Ipilimumab as sequential therapy did not appear to improve OS and was associated with more severe irAE than PD-1 blockade monotherapy. We need to carefully consider treating patients with poor PS and low ALC.

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