Risk factors for immune-related adverse events associated with anti-PD-1 pembrolizumab

Sci Rep. 2019 Oct 1;9(1):14039. doi: 10.1038/s41598-019-50574-6.

Abstract

We investigated risk factors for immune-related adverse events (irAEs) in patients treated with anti-programmed cell death protein1 antibody pembrolizumab. A retrospective medical record review was performed to identify all patients who received at least one dose of pembrolizumab at Samsung Medical Center, Seoul, Korea between June 2015 and December 2017. Three hundred and ninety-one patients were included in the study. Data were collected on baseline characteristics, treatment details, and adverse events. Univariate and multivariate logistic regression models were used to identify risk factors for irAEs. Sixty-seven (17.1%) patients experienced clinically significant irAEs; most commonly dermatologic disorders, followed by pneumonitis, musculoskeletal disorders, and endocrine disorders. Fourteen patients (3.6%) experienced serious irAEs (grade ≥ 3). Most common serious irAEs were pneumonitis (2.3%). Four deaths were associated with irAEs, all of which were due to pneumonitis. In multivariate regression analysis, a higher body mass index (BMI) and multiple cycles of pembrolizumab were associated with higher risk of irAEs (BMI: odds ratio [OR] 1.08, 95% confidence interval [CI] 1.01-1.16; pembrolizumab cycle: OR 1.15, 95% CI 1.08-1.22). A derived neutrophil-lymphocyte ratio (dNLR) greater than 3 at baseline was correlated with low risk of irAEs (OR 0.37, 95% CI 0.17-0.81). Our study demonstrated that an elevated BMI and higher number of cycles of pembrolizumab were associated with an increased risk of irAEs in patients treated with pembrolizumab. Additionally, increased dNLR at baseline was negatively correlated with the risk of developing irAEs.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / immunology
  • Antineoplastic Agents, Immunological / adverse effects*
  • Endocrine System Diseases / chemically induced
  • Endocrine System Diseases / immunology
  • Female
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Musculoskeletal Diseases / chemically induced
  • Musculoskeletal Diseases / immunology
  • Pneumonia / chemically induced
  • Pneumonia / immunology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology
  • Republic of Korea
  • Retrospective Studies
  • Risk Factors
  • Skin Diseases / chemically induced
  • Skin Diseases / immunology
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • pembrolizumab