Immune checkpoint inhibitor–related endocrinopathies: Real-world assessment strategies and best practices.

Abstract

488 Background: Immune checkpoint inhibitors (ICI)-related endocrinopathies are among the most clinically significant immune-related adverse events (irAEs). Despite their frequent occurrence, reliable real-world data on their characterization and grading are limited. Inconsistencies in clinical documentation, reporting, and toxicity grading present challenges for accurately capturing endocrine irAEs. This abstract describes our methodology and toxicity assessment framework, used to characterize endocrine toxicities in patients receiving ICIs, with the goal of establishing reproducible best practices. Methods: We used data collected from the (DiRECT), a nationwide, multicenter, prospective observational cohort study of adult cancer patients receiving FDA-approved anti-PD-1/-L1 agents, across URCC NCORP – affiliated institutions. ICI-related endocrinopathies were identified through a systematic review of baseline and periodic clinical assessment notes, laboratory values, and treatment records. Toxicity grading was assigned and checked using the CTCAE v5.0 guidelines as the primary standard; NCCN and Endocrine Society guidelines served as supplementary standards when CTCAE were insufficient. A structured review of endocrinopathies was conducted at each infusion cycle for the first 6 months and thereafter periodically. Data completeness and consistency in endocrinopathy records were ensured through a two-phase cleaning and audit protocol. Phase 1 addresses missing data, and phase 2 is a clinically oriented review to standardize endocrinopathy CTCAE classification and to reconcile ICI exposure with the patient care team and clinical notes to confirm attribution. Quality was further assessed through an internal audit and external validation against published data on incidence, type, severity, and risk factors. Results: Among 932 patients with analyzable data and a median follow-up of 12 months from enrolment who completed at least phase 1 of the clinical review, the audit process identified under-reporting and grading misclassification as the major issues. In our subset, 204 (21.8%) patients have developed any-grade endocrinopathies, the majority of which were grade 1. Thyroid dysfunction was the most consistently documented endocrinopathy, while adrenal insufficiency and hypopituitarism showed more variability in documentation and CTCAE grade assignment. Laboratory monitoring also varied across participating sites. Conclusions: A standardized, multi-step data review and toxicity-grading audit is essential for accurate real-world assessment of ICI-related endocrinopathies. This framework provides a reliable, and reproducible approach for future observational studies and may help bridge the gap between clinical documentation practices and established guideline-based standards of care. Clinical trial information: NCT05364086 .