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Immune checkpoint inhibitors and immune-related adverse events
PD-1, PD-L1 and CTLA-4 inhibitors release the brakes on T cells against the tumour, so they may cause autoimmune inflammation in any organ; management is set by grade — continue, hold or steroids — and in resistant cases infliximab or mycophenolate.
Why it matters in the exam
Immunotherapy is now part of treatment for most cancers, and its side effects are asked in the exam every year. The typical stem shows a patient on nivolumab or ipilimumab with diarrhoea, headache and fatigue, rash, acute hyperglycaemia or dyspnoea, and asks for the diagnosis and the treatment.
It is important to distinguish effects more typical of CTLA-4 inhibitors — colitis and inflammation of the pituitary — from effects more typical of PD-1 inhibitors — pneumonitis and thyroiditis. Questions also ask about markers that predict response (PD-L1, MSI-high, high tumour mutational burden) and about distinguishing pseudoprogression from true progression.
Key points
- Checkpoint inhibitors cause autoimmune inflammation in any organ, so every new symptom in such a patient requires thinking of an immune effect.
- Colitis and hypophysitis are more common with CTLA-4, and pneumonitis and thyroiditis are more common with PD-1.
- Treatment by grade: grade 1 — continue; grade 2 — hold and give prednisone; grade 3 to 4 — stop and give methylprednisolone.
- Steroid resistance: infliximab or vedolizumab in the bowel, and mycophenolate in the liver.
- Myocarditis is rare but lethal, and requires high-dose steroids and permanent discontinuation.
Summary table
| System | Presentation | Treatment |
|---|---|---|
| Bowel | Diarrhoea and colitis — more common with CTLA-4 and with the combination | Grade 2 or higher: hold and give prednisone; steroid-refractory — infliximab or vedolizumab; exclude CMV and infection |
| Endocrine glands | Hypophysitis (CTLA-4) — headache and low ACTH; thyroiditis (PD-1) — hyperthyroidism then hypothyroidism; type 1 diabetes with DKA | Hormone replacement; immunotherapy can usually continue; if adrenal insufficiency is suspected — hydrocortisone before thyroxine |
| Lung | Cough and dyspnoea with opacities; more common with PD-1 and in lung cancer | Grade 2: hold and give prednisone; grade 3 or higher: methylprednisolone in hospital |
| Liver | Raised liver enzymes | Steroids; refractory — mycophenolate (not infliximab) |
| Heart and muscle | Myocarditis, sometimes with myositis and myasthenia; rare and lethal | Permanent discontinuation and high-dose methylprednisolone; troponin, ECG and echo |
| Skin and joints | Rash, itch, vitiligo; arthritis | Topical treatment and steroids by grade |
| General principles by grade | Grade 1 — continue with monitoring; grade 2 — hold and give prednisone 0.5 to 1 mg per kg; grade 3 to 4 — stop and give methylprednisolone 1 to 2 mg per kg | Taper steroids gradually over at least 4 to 6 weeks |
In the full version for subscribers
- A simple algorithm
- Memory aid
- Exam traps
- 5 review cards
- Enough for IMLE
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Sources
- ASCO Guideline: Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy, 2021 — Organ-specific recommendations
- ESMO Clinical Practice Guideline: Management of toxicities from immunotherapy, 2022 — Diagnosis, treatment and follow-up
- NCCN Clinical Practice Guidelines in Oncology: Management of Immunotherapy-Related Toxicities, 2026 — General principles
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-06. The text may contain errors; when in doubt, check the source.