Longitudinal Cohort Study of Immune-Related Adverse Events in Solid Tumor Patients Treated With Immune Checkpoint Inhibitors

Immune checkpoint inhibitors targeting CTLA-4, PD-1, and PD-L1 pathways have demonstrated substantial clinical benefit across multiple solid malignancies. However, their mechanism of action can also lead to immune-related adverse events (irAEs), which may involve dermatologic, gastrointestinal, hepatic, pulmonary, endocrine, musculoskeletal, cardiovascular, renal, hematologic, neurological, and psychiatric systems. Neurological and neurocognitive irAEs, in particular, are uncommon but potentially devastating and remain poorly characterized.

This study is a hybrid prospective longitudinal observational cohort designed to move beyond reactive identification of irAEs toward proactive prediction and mechanistic understanding. Adult patients with solid tumors initiating a new ICI regimen are enrolled prior to treatment initiation. Longitudinal clinical data, imaging, and biospecimens are collected at predefined intervals and at the time of suspected irAE onset when feasible.

Participants are assigned to event-defined cohorts based on the first grade ≥2 irAE that drives clinical management, including neuro-sensory, gastrointestinal/hepatic, rheumatologic/musculoskeletal, vascular/renal, hematologic, multi-organ, or control (no significant irAE) cohorts. Deep phenotyping and multi-omics analyses-including immune cell profiling, proteomics, metabolomics, and microbiome analyses-are performed to identify biomarkers associated with irAE risk, severity, and outcomes.

• Neuro-Sensory irAE Subgroup: Proportion of Participants with Modified Rankin Scale (mRS) Score ≤2 [Срок оценки: 12 weeks after irAE diagnosis]
• Neuro-Sensory irAE Subgroup:Proportion of Participants with Objective Improvement on Nerve Conduction Studies [Срок оценки: 12 weeks after irAE diagnosis]
• Psychiatric and Cognitive irAE Subgroup:Proportion of Participants with Patient Health Questionnaire-9 (PHQ-9) Score <10 [Срок оценки: 8 weeks after initiation of targeted treatment]
• Psychiatric and Cognitive irAE Subgroup:Proportion of Participants with ≥0.5 Standard Deviation Improvement on ≥2 Standardized Neuropsychological Tests [Срок оценки: 12 weeks after irAE diagnosis]
• Gastrointestinal and Hepatic irAE Subgroup: Proportion of Participants with ≤3 Bowel Movements per Day and No Hematochezia [Срок оценки: 2 weeks after initiation of immunosuppressive therapy]
• Gastrointestinal and Hepatic irAE Subgroup: Proportion of Participants with Alanine Aminotransferase (ALT) ≤1.5 × Upper Limit of Normal [Срок оценки: 4 weeks after initiation of immunosuppressive therapy]
• Rheumatologic and Musculoskeletal irAE Subgroup: Proportion of Participants with Clinical Disease Activity Index (CDAI) ≤10 [Срок оценки: 12 weeks after initiation of immunosuppressive therapy]
• Rheumatologic and Musculoskeletal irAE Subgroup: Proportion of Participants with ≥20% Improvement in Manual Muscle Testing (MMT-8) Score [Срок оценки: 12 weeks after irAE diagnosis]
• Renal irAE Subgroup: Proportion of Participants with Serum Creatinine Recovery to Within 1.3 × Baseline [Срок оценки: 12 weeks after irAE diagnosis]
• Hematologic irAE Subgroup: Proportion of Participants with Sustained Hematologic Response (CTCAE v5.0 Grade ≤1 for ≥4 Weeks) [Срок оценки: Within 12 weeks after initiation of first-line immunosuppressive therapy]
• Hematologic irAE Subgroup: Proportion of Participants with Normalized Lactate Dehydrogenase and Stable Hemoglobin [Срок оценки: 2 weeks after initiation of treatment]
• Multi-Organ irAE Subgroup: Proportion of Participants without Any New or Worsening ≥Grade 3 Immune-Related Adverse Events Across Organ Systems [Срок оценки: Within 4 weeks after initiation of combined immunosuppressive therapy]