The immune-related symptom web in immune checkpoint inhibitor therapy: a longitudinal clinical safety surveillance framework for immune-related adverse events

Immune checkpoint inhibitors (ICIs) produce durable antitumor activity by releasing inhibitory immune pathways, but the same pharmacology can disrupt peripheral tolerance and generate immune-related adverse events (irAEs) that are delayed, recurrent, chronic, multisystem, and clinically nonspecific. Organ-specific guidelines are indispensable once toxicity is suspected; however, clinical surveillance commonly begins with an undifferentiated patient report or an objective abnormality rather than a confirmed organ diagnosis. This narrative review integrates clinical pharmacology, immunobiology, guidelines, pharmacovigilance principles, patient-reported outcome research, digital monitoring studies, and multidisciplinary implementation evidence. Focused, non-systematic searches of PubMed/MEDLINE and the Cochrane Library, supplemented by current guidelines and official regulatory sources, were finalized on 18 July 2026; representative strategies, an evidence-provenance map, and a structured comparison with existing approaches are provided in the Supplementary Material. We define an individual-level safety alert as a new symptom, functional change, laboratory abnormality, physiological change, imaging finding, or other clinically meaningful observation requiring contextual assessment. It is not equivalent to a formal population-level pharmacovigilance signal. The immune-related symptom web is a symptom-centered but not symptom-exclusive model that organizes exposure chronology, individual baseline, symptom and objective-data combinations, trajectories, competing diagnoses, corticosteroid tapering, discontinuation, rechallenge, and consequence-weighted urgency. The Signal-Attribution-Escalation-Longitudinal Management (SAELM) framework translates this information structure into an accountable workflow from alert capture to attribution, escalation, guideline-linked management, documentation, and reassessment. Its novelty lies in integrating and longitudinally organizing existing components rather than inventing each component. The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and electronic patient-reported outcome (ePRO) systems are positioned as capture and communication tools, not diagnostic or causal instruments. The models remain conceptual and hypothesis-generating. The most feasible first validation study is a prospective multicenter observational cohort with independent clinical adjudication; the primary safety outcome should be the false-negative proportion for severe or organ-threatening irAEs, accompanied by alert burden, response time, and potentially avoidable urgent escalation.