01Purpose and principlesWhat the treatment does and how it fits into care.
Checkpoint blockade increases antitumour immunity but removes normal protection against autoimmunity. Tumour response varies by antigenicity, immune microenvironment and biomarkers; a biomarker changes probability rather than guaranteeing benefit. Combination checkpoint therapy may improve efficacy in some settings while increasing immune toxicity. Consent must include unpredictable timing, potential permanence and the need for urgent assessment across specialties.
Immune toxicity commonly affects skin, bowel, liver, lungs, thyroid, pituitary, adrenal glands and joints, but cardiac, neurological, renal, ocular and haematological events may be rapidly fatal. Infection, tumour progression and other medicines often mimic the presentation and can coexist, especially after immunosuppression. A normal single blood test does not exclude evolving myocarditis or pneumonitis when symptoms progress.
Management is organ- and grade-specific. Treatment is held for significant toxicity; corticosteroids are used promptly for many moderate or severe events, with additional immunosuppression when refractory. Endocrine deficiencies are generally replaced and may be permanent. Rechallenge is a multidisciplinary decision based on organ, severity, recovery, alternative therapy and previous cancer benefit.
Key points
- PD-1, PD-L1 and CTLA-4 pathways restrain T-cell activation; checkpoint inhibitors release that restraint and can produce durable tumour control in selected cancers.
- Eligibility depends on tumour type, stage, treatment line and sometimes PD-L1, mismatch-repair or other biomarkers under the current protocol.
- Immune-related adverse events can affect any organ, appear after one dose or months after stopping, and involve several systems simultaneously.
- The initial action for suspected clinically important immune toxicity is to hold checkpoint treatment, grade severity and investigate immune, infective, malignant and medicine causes together.
- Corticosteroids are first-line treatment for many significant immune toxicities, but dose, route and taper depend on organ and severity; endocrine hormone loss often needs replacement rather than recovery.
- Myocarditis, myositis and myasthenic features can overlap and deteriorate rapidly despite modest early symptoms.
- Before giving thyroid hormone for possible hypophysitis, assess and protect the cortisol axis because unrecognised ACTH deficiency can precipitate crisis.
- Provide a treatment alert card and 24-hour contact, and tell every acute service about previous checkpoint exposure even after therapy ends.
02Indications, selection and cautionsWho may benefit, who needs urgent treatment and important alternatives.
New cough, breathlessness, hypoxia or interstitial imaging change requires urgent exclusion of infection, embolism and progression.
Increasing stool frequency, abdominal pain, blood, fever or dehydration can progress to perforation and should be graded from baseline.
Headache, fatigue, hypotension, hyponatraemia, polyuria or glucose disturbance may indicate pituitary, adrenal, thyroid or pancreatic injury.
Ptosis, dysphagia, proximal weakness, myalgia, chest pain or troponin elevation can combine myositis, myasthenia and myocarditis.
A new inflammatory syndrome remains treatment-related months after the last dose and must not be excluded solely by timing.
03Assessment before treatmentTests and checks that guide safe selection.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Baseline full blood count and organ profileFirst step - Why
- Establish marrow, renal, hepatic, glucose and electrolyte status before therapy.
- Interpretation and limitations
- Repeat with symptoms and cycles; trends and multisystem abnormalities can reveal toxicity before severe organ failure.
- 02
Thyroid and cortisol-axis tests - Why
- Identify baseline or treatment-related endocrine dysfunction.
- Interpretation and limitations
- Interpret paired hormones and clinical state; suspected adrenal crisis is treated immediately without waiting for a definitive dynamic test.
- 03
ECG, troponin and creatine kinase - Why
- Assess possible myocarditis and neuromuscular overlap.
- Interpretation and limitations
- Any concerning symptom or abnormality merits urgent cardio-oncology and neurological assessment; a single normal value may not end evaluation.
- 04
Chest imaging and oxygenation - Why
- Evaluate cough, dyspnoea or hypoxia.
- Interpretation and limitations
- CT pattern can support pneumonitis but infection, embolism and progression require parallel assessment and sometimes bronchoscopy.
- 05
Stool, inflammatory and endoscopic assessment - Why
- Separate immune colitis from infection and define severity.
- Interpretation and limitations
- Obtain infection testing without delaying treatment of severe physiology; imaging or endoscopy is selected with gastroenterology for complicated disease.
04Treatment approachPreparation, options, escalation and aftercare.
01BaselinePrepare for immune treatmentFirst stepA patient is due to start checkpoint blockade.+
- 1Confirm tumour indication, biomarker where required, autoimmune and transplant history, organ baseline and interacting immunosuppression.
- 2Explain organ-specific warning symptoms, delayed events, alert-card use and the 24-hour acute-oncology route.
- 3Record baseline bowel, respiratory, neurological, endocrine, skin and musculoskeletal status to make later change interpretable.
02SuspectHold and investigate toxicityA new inflammatory, endocrine or organ symptom occurs during or after therapy.+
- 1Hold checkpoint treatment for clinically important suspected toxicity and grade from baseline while assessing ABCDE physiology.
- 2Investigate immune toxicity, infection, thrombosis, progression and other medicines in parallel with early organ-specialist and acute-oncology input.
- 3Start protocol-led corticosteroid or hormone replacement promptly when indicated, giving emergency hydrocortisone before thyroid hormone if cortisol failure is possible.
03ResolveTaper, replace and reconsiderThe acute event improves or proves refractory.+
- 1Taper corticosteroid over the organ-specific period and add specialist immunosuppression when response is inadequate or steroid toxicity becomes important.
- 2Provide infection and bone or gastric protection appropriate to immunosuppression, and continue permanent endocrine replacement where recovery is unlikely.
- 3AlternativeDecide rechallenge in MDT using severity, organ, residual deficit, alternative treatment and previous cancer benefit; document lifelong alert advice.
05Regimens, contraindications and interactionsTreatment details and the circumstances that modify them.
Pembrolizumab
200 mg intravenously every 3 weeks or 400 mg every 6 weeks, infused over 30 minutes, for a licensed and funded indication. Do not reduce the dose; hold or discontinue according to organ toxicity, severity and the product and treatment protocol.Immune toxicity can affect any organ during or after treatment. Establish baseline function, give lifelong alert advice, assess infection and progression in parallel, and protect cortisol before starting thyroid replacement when adrenal or pituitary failure is possible.
06Complications, monitoring and follow-upAdverse effects, response and longer-term review.
- Check symptoms and organ-specific blood tests before each dose and continue surveillance after treatment because delayed toxicity occurs.
- During acute toxicity trend the physiological endpoint, such as oxygenation, stool frequency, troponin, transaminases, creatinine or hormone status.
- Monitor corticosteroid response and harms, infection risk and taper adherence, escalating promptly when improvement does not occur at the expected time.
- Maintain permanent documentation of immune toxicity and endocrine replacement across primary, emergency and specialist records.
- If rechallenged, define a lower threshold for repeat assessment and a clear stop plan before the next infusion.
07Special situationsVariants, exceptions and circumstances that change the usual approach.
Any organ can inflame
A symptom outside the common skin, bowel and thyroid patterns can still be immune-related and deserves mechanism-aware assessment.
Infection can coexist
Steroid treatment and cancer increase infection risk, so cultures and antimicrobial care may proceed alongside immune suppression.
Endocrine loss differs
Inflamed pituitary, thyroid or pancreas may leave permanent hormone deficiency even after systemic symptoms settle.
Overlap predicts danger
Myocarditis with myositis or myasthenic features can deteriorate rapidly and needs joint cardiac, neurological and critical-care action.
Timing is wide
Toxicity can begin after therapy has stopped, so past checkpoint exposure remains relevant in every acute history.
08Common pitfallsFrequent interpretation and management errors.
- 01
Excluding toxicity because treatment ended.
- 02
Starting thyroid hormone before protecting cortisol.
- 03
Calling pneumonitis without assessing infection and embolism.
- 04
Missing myocarditis in a weak patient.
- 05
Tapering corticosteroid too rapidly in clinical practice.
- 06
Restarting checkpoint treatment without MDT review.