Chapter 34, Ep 4 of 4: Immune Checkpoint Inhibitor Toxicity

Episode four closes the module on checkpoint inhibitor toxicity, one entity with many organ targets, where releasing the brakes on T cells means the same cells recognize self. Drug class predicts the toxicity rate, with anti-CTLA-4 broad and severe, anti-PD-1 focal and milder, and combination highest, while grade drives therapy through a universal seventy-two-hour escalation window. The colitis algorithm runs grade-based steroids then infliximab or vedolizumab, with the choice turning on hepatic comorbidity and CMV risk. The single most tested distinction is that steroid-refractory hepatitis goes to mycophenolate mofetil, not infliximab, because infliximab is contraindicated by its own hepatotoxicity, and the whole framework extends to pneumonitis, endocrinopathies, and the other immune-related adverse events.   Topics covered Checkpoint biology and the CTLA-4 versus PD-1 distinction Colitis rates by drug class and onset windows Colitis recognition, mimics, and endoscopic predictors Grade-based colitis management and the seventy-two-hour window Infliximab versus vedolizumab and CMV risk Checkpoint hepatitis workup and the autoimmune contrast Mycophenolate replacing infliximab in hepatitis The irAE framework across organ systems   Key decisions Exclude Clostridioides difficile before any steroid escalation in every checkpoint colitis patient, and add CMV testing in anyone already steroid- or biologic-pretreated. Grade colitis by stools above baseline: grade one gets loperamide with the drug continued, grade two holds the drug and starts budesonide or prednisone, grade three to four discontinues anti-CTLA-4 and starts intravenous methylprednisolone. Use the seventy-two-hour response window as the universal escalation trigger, adding a biologic when the diffuse T-cell infiltrate escapes steroid effect. Choose vedolizumab over infliximab when there is hepatic dysfunction or active immune-mediated hepatitis, because it is gut-selective and spares systemic anti-CMV immunity. Give steroid-refractory checkpoint hepatitis mycophenolate mofetil one gram twice daily, because infliximab is contraindicated by immune-mediated hepatotoxicity. Treat CMV reactivation during a prednisone taper with intravenous ganciclovir and defer infliximab while CMV is active, since anti-TNF therapy precipitates fulminant viremic disease. Manage endocrine immune-related adverse events with hormone replacement rather than steroid taper, because the gland is already irreversibly damaged by the time it is recognized.   For the full chapter with MCQs, tables, and primary-guideline references, visit www.boardpearls.com. Questions or feedback: [email protected]. (00:00) - One entity, many organ targets (01:06) - CTLA-4 versus PD-1 and the toxicity rates (02:28) - Colitis: rates, onset, and recognition (04:40) - Grade-based colitis management (06:22) - Infliximab versus vedolizumab (09:53) - Checkpoint hepatitis and the mycophenolate swap (13:16) - Why infliximab is contraindicated in hepatitis (16:29) - The irAE framework across organ systems