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← Oncology and palliative care indexChapter sections
Purpose and principlesIndications, selection and cautionsAssessment before treatmentTreatment approachRegimens, contraindications and interactionsComplications, monitoring and follow-upSpecial situationsCommon pitfallsQuestionsSources
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Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.

Immune-checkpoint inhibitors

Oncology and palliative care · UK scope · Sources checked 27 Aug 2026 · Clinical review pending

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Time-critical presentation

New chest pain, dyspnoea, weakness, dysphagia, confusion, severe headache, visual change, jaundice, profuse diarrhoea, hypotension or marked glucose disturbance during or after checkpoint therapy may represent myocarditis, pneumonitis, neurological toxicity, colitis, hepatitis or endocrine crisis. Hold treatment, involve acute oncology and the relevant organ team, and investigate infection and progression in parallel.

Purpose and principles

Explain checkpoint blockade and tumour selection, obtain a safe multisystem baseline, distinguish immune toxicity from infection or progression, and coordinate prompt treatment without masking endocrine emergencies.

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.

Indications, selection and cautions

Immune pneumonitis

New cough, breathlessness, hypoxia or interstitial imaging change requires urgent exclusion of infection, embolism and progression.

Immune colitis

Increasing stool frequency, abdominal pain, blood, fever or dehydration can progress to perforation and should be graded from baseline.

Endocrine toxicity

Headache, fatigue, hypotension, hyponatraemia, polyuria or glucose disturbance may indicate pituitary, adrenal, thyroid or pancreatic injury.

Overlap neuromuscular syndromeRed flag

Ptosis, dysphagia, proximal weakness, myalgia, chest pain or troponin elevation can combine myositis, myasthenia and myocarditis.

Delayed immune event

A new inflammatory syndrome remains treatment-related months after the last dose and must not be excluded solely by timing.

Assessment before treatment

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 05
    Stool, inflammatory and endoscopic assessment

Treatment approach

01BaselinePrepare for immune treatmentFirst stepA patient is due to start checkpoint blockade.+
  1. 1Confirm tumour indication, biomarker where required, autoimmune and transplant history, organ baseline and interacting immunosuppression.
  2. 2Explain organ-specific warning symptoms, delayed events, alert-card use and the 24-hour acute-oncology route.
  3. 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.+
  1. 1Hold checkpoint treatment for clinically important suspected toxicity and grade from baseline while assessing ABCDE physiology.
  2. 2Investigate immune toxicity, infection, thrombosis, progression and other medicines in parallel with early organ-specialist and acute-oncology input.

Regimens, contraindications and interactions

PD-1 blockade for selected tumour and biomarker contexts; indication and line determine whether it is used alone or with other anticancer treatment.

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.

Complications, monitoring and follow-up

  • 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.

Special situations

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.

Common pitfalls

  1. 01

    Excluding toxicity because treatment ended.

  2. 02

    Starting thyroid hormone before protecting cortisol.

  3. 03

    Calling pneumonitis without assessing infection and embolism.

  4. 04

    Missing myocarditis in a weak patient.

  5. 05

    Tapering corticosteroid too rapidly in clinical practice.

  6. 06

    Restarting checkpoint treatment without MDT review.

Practice

Two practice questions

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Oncology and palliative careOriginal SBA

Checkpoint endocrine sequence

A patient on checkpoint therapy has headache, hypotension, hyponatraemia and low free thyroid hormone with an inappropriately normal TSH. What is the immediate endocrine safety principle?

Choose one answer, then submit
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Sources and review status6 sources · checked 27 Aug 2026 · clinical review pending+
Sources

Sources and review status

National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.

  • MHRA Safety Roundup: checkpoint inhibitor overlap syndromesPotentially fatal myocarditis with myositis or myasthenia gravis overlap.
  • NHS England adult cancer chemotherapy service specificationCurrent requirements for safe, protocol-governed systemic anticancer treatment services.
  • NHS England cancer programmeAcute oncology and multidisciplinary management of complex treatment toxicity.
  • NICE shared decision making recommendationsConsent for uncertain benefit, delayed toxicity and rechallenge decisions.
  • Pembrolizumab Summary of Product CharacteristicsLicensed schedules, no-dose-reduction approach and organ-specific hold or discontinuation requirements.
  • Society for Endocrinology checkpoint endocrine emergenciesEmergency endocrine assessment, cortisol-first sequencing and hormone replacement during checkpoint therapy.

Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes

Authoring stateComplete draft

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.
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.
  • 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.+
    1. 1Taper corticosteroid over the organ-specific period and add specialist immunosuppression when response is inadequate or steroid toxicity becomes important.
    2. 2Provide infection and bone or gastric protection appropriate to immunosuppression, and continue permanent endocrine replacement where recovery is unlikely.
    3. 3AlternativeDecide rechallenge in MDT using severity, organ, residual deficit, alternative treatment and previous cancer benefit; document lifelong alert advice.
    Clinical stateAwaiting review
    JurisdictionUnited Kingdom