Background/Purpose: Immune checkpoint inhibitors have been established as a novel standard treatment for various types of malignancies. However, these new class of drugs have led to increased immune-related adverse events (irAEs) including rheumatic manifestations.
The aim of this study was to determine the risk factors of irAEs in patients treated with anti-programmed death 1 antibody pembrolizumab.

Methods: 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 identified. Multivariate logistic regression model was used to identify risk factors of irAEs.

Results: The median number of cycles of pembrolizumab was two (range, 1-36). The primary malignancies included in the study were lung cancer (n=211, 54.0%), melanoma (n=74, 18.9%), lymphoma (n=53, 13.6%) and others (n=53, 13.6%). Sixty-seven (17.1%) patients experienced clinically significant irAEs; most commonly dermatologic disorders (n=39, 10.0%), pneumonitis (n=11, 2.8%), musculoskeletal disorders (n=10, 2.6%), followed by endocrine disorders (n=7, 1.8%). Fourteen patients (3.6%) experienced serious irAEs (≥ grade 3). Most common serious irAEs were pneumonitis (n=9, 2.3%). There were 4 deaths associated with irAEs, all of which were due to pneumonitis. In univariate logistic regression analysis, body mass index, number of cycles and cumulative dose of pembrolizumab, and baseline neutrophil-lymphocyte ratio were the risk factors of irAEs in pembrolizuamb-treated patients. Multivariate logistic regression analysis was performed with variables that were significant in univariate analysis. Higher body mass index and multiple cycles of pembrolizumab were associated with higher risk of irAEs (body mass index: odds ratio [OR] 1.080, 95% confidence interval [95% CI] 1.005-1.161, P = 0.035; pembrolizumab cycle: OR 1.153, 95% CI 1.087-1.224, P < 0.001). Low neutrophil-leukocyte ratio tended to increase irAE risk, but not statistically significant in multivariate analysis (OR 0.953, 95% CI 0.902-1.007, P = 0.089).

Conclusion: To our knowledge, this is the first study to explore the risk factor for irAE in patients undergoing modern cancer immunotherapy. Our study demonstrate that BMI is associated with an increased risk of irAEs in patients treated with pembrolizumab. Also, the number of cycles of pembrolizumab was a risk factor for the development of irAEs. Further studies to investigate the potential mechanisms by which obesity raises irAEs are needed.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-factors-of-immune-related-adverse-events-in-patients-treated-with-anti-programmed-cell-death-1-antibody-pembrolizumab/