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irAERespiratoryICD-10 J84.x

ICI-related pneumonitis

Immune-mediated pneumonitis ยท checkpoint-inhibitor pneumonitis

ICI-related pneumonitis is a serious immune-related adverse event affecting 3-5% of patients on anti-PD-1 monotherapy and up to 10% on combination ICI. It carries one of the highest fatality rates among irAEs (5-10% in severe cases). Five radiological patterns are recognised: COP-like, ground-glass, hypersensitivity-like, interstitial and acute-interstitial. ESMO and ATS / BTS guidelines underpin management; prompt steroid intervention is critical to prevent progression to respiratory failure.

CurrentLast reviewed 16 May 2026

Epidemiology

  • Incidence (any grade):
    • Anti-PD-1 monotherapy: 3-5%; G3+ 1-2%.
    • Anti-CTLA-4 monotherapy: 1-2%.
    • Combination ICI: 7-10%; G3+ 3-5%.
    • NSCLC patients: higher risk than other cancers.
  • Onset: median 2.5-3 months but ranges from days to >12 months.
  • Mortality: 5-10% in severe (G3+) disease.
  • Risk factors:
    • Pre-existing lung disease (COPD, ILD, pulmonary fibrosis).
    • Prior thoracic radiotherapy.
    • Smoking history.
    • Combination ICI.
    • Concurrent or prior chemotherapy.

Radiological patterns

  • Cryptogenic organising pneumonia (COP)-like: peripheral / subpleural consolidation; reverse halo sign; commonest pattern.
  • Ground-glass opacities (GGO): diffuse / patchy.
  • Hypersensitivity pneumonitis-like: centrilobular nodules.
  • Non-specific interstitial pneumonia (NSIP): subpleural sparing.
  • Acute interstitial pneumonia / ARDS-like: diffuse alveolar damage; high mortality.

Clinical features

  • Cough (dry).
  • Dyspnoea on exertion, then at rest.
  • Chest pain.
  • Fever.
  • Hypoxia, desaturation.
  • Asymptomatic radiological pneumonitis (~30%) โ€” identified on imaging.
  • Differential: infection (bacterial, viral, PCP), pulmonary embolism, tumour progression, lymphangitic carcinomatosis, cardiac failure.

CTCAE grading

GradeFeaturesAction
G1Asymptomatic; radiological onlyHold ICI; reassess imaging in 1-2 weeks; restart when resolved.
G2Symptomatic; mild-moderate; limits instrumental ADLHold ICI; prednisolone ~1 mg/kg/day (up to 2 mg/kg/day if not improving); consider hospitalisation; reassess in 48-72 h.
G3Severe symptoms; limits self-care; oxygen indicated; hospitalisationPermanently discontinue ICI; IV methylprednisolone 2-4 mg/kg/day; admit; respiratory team.
G4Life-threatening; respiratory failure; ICU; mechanical ventilationPermanently discontinue ICI; IV methylprednisolone 4 mg/kg/day; ICU; consider MMF, infliximab, IVIG.

Workup

  • Detailed history: respiratory symptoms onset, severity, exertional vs rest, productive cough.
  • Examination: respiratory rate, SpO2, auscultation (crackles), tachycardia.
  • Bloods: FBC, CRP, U&E, LFT, lactate, ABG, BNP.
  • Sputum / blood cultures; viral PCR (influenza, RSV, COVID); HIV; ฮฒ-D-glucan / Aspergillus / PCP if immunosuppressed.
  • Imaging: CT chest (high-resolution) โ€” preferred over CXR; characterise pattern.
  • Bronchoscopy ยฑ BAL if diagnostic uncertainty; exclude infection (PCP, viral, bacterial, fungal); cytology rules out tumour.
  • Pulmonary function tests: DLCO reduced.
  • Respiratory medicine consultation for G2+.

Management

  • G1: hold ICI; reassess CT in 1-2 weeks; restart if resolved.
  • G2:
    • Hold ICI.
    • Prednisolone ~1 mg/kg/day (up to 2 mg/kg/day if not improving) with taper over 6-8 weeks.
    • PPI, calcium / vitamin D, PCP prophylaxis if >4 weeks on steroids.
    • Reassess at 48-72 hours.
    • ICI may be resumed after full recovery to grade ≤ 1 (specialist decision).
  • G3:
    • Permanently discontinue ICI — rechallenge is not recommended after grade 3–4 pneumonitis (ESMO / ASCO).
    • IV methylprednisolone 2-4 mg/kg/day.
    • Admit; respiratory medicine team.
    • If no improvement in 48-72 h โ†’ mycophenolate mofetil 500-1000 mg BD or infliximab 5 mg/kg.
  • G4:
    • Permanently discontinue ICI.
    • IV methylprednisolone 4 mg/kg/day.
    • ICU; ventilatory support.
    • MMF + infliximab + IVIG combination in refractory cases.
    • Consider tocilizumab or cyclophosphamide.
  • Slow steroid taper over 6-12 weeks to prevent relapse.
  • PCP prophylaxis (co-trimoxazole 480 mg OD) for prolonged steroid >4 weeks.
  • NHSE / NICE / ESMO consensus: respiratory medicine MDT input mandatory for G3+.

References

  1. Haanen J et al. ESMO Clinical Practice Guideline for immune-related adverse events. Ann Oncol. 2022;33:1217-1238.
  2. Schneider BJ et al. ASCO clinical practice guideline update: management of immune-related adverse events. J Clin Oncol. 2021;39:4073-4126.
  3. Naidoo J et al. Pneumonitis in patients treated with anti-PD-1/PD-L1 therapy. J Clin Oncol. 2017;35:709-717.
  4. Nishino M et al. Anti-PD-1-related pneumonitis during cancer immunotherapy. N Engl J Med. 2015;373:288-290.
  5. British Thoracic Society. Guidelines for ICI-related pneumonitis management. London: BTS; 2023.

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