Pembrolizumab-Induced Sarcoidosis-Like Immune-Related Adverse Events: A Pooled Analysis of Published Cases and Report of a Novel Manifestation Involving Phosphocalcic Metabolism.
TL;DR
Pembrolizumab-induced DISR is a rare irAE driven by immune dysregulation, and this case expands its clinical spectrum by identifying a novel manifestation of macrophage-mediated calcium dysregulation.
Abstract
Immune checkpoint inhibitors such as pembrolizumab can trigger immune-related adverse events, including rare sarcoidosis-like reactions (DISR), whose immunopathogenesis and clinical spectrum remain incompletely defined. We conducted a systematic review of all published cases of pembrolizumab-induced DISR, extracted and descriptively analyzed clinical, laboratory, imaging, and outcome data from 41 patients, and additionally report a 42-year-old woman who developed multiorgan DISR with a previously unreported metabolic complication involving dysregulated calcium homeostasis and ureteral double-J stent calcification. The median age at onset was 65 years, with melanoma as the most frequent underlying malignancy. Lymph nodes, lungs, and skin were the most commonly affected organs, and the median time to onset was 16 weeks, with some cases occurring after treatment discontinuation. ACE levels were elevated in 60% of cases, PET/CT showed increased FDG uptake in 95% of cases, and histologic confirmation was obtained in nearly all patients. Corticosteroids were the most frequent treatment, and 90.5% achieved stable disease or remission. Pembrolizumab-induced DISR is a rare irAE driven by immune dysregulation, and our case expands its clinical spectrum by identifying a novel manifestation of macrophage-mediated calcium dysregulation. Our pooled analysis of all published cases to date contributes to a broader understanding of this underrecognized entity. Early recognition is essential to avoid misdiagnosis of tumor progression, and DISR may serve as a potential biomarker of effective antitumor immune activation.