Symptom Grade

Grade 1

  • Radiographic changes only
  • Ground glass change, non-specific interstitial pneumonia

Grade 2

  • Mild/moderate new symptoms
  • Dyspnoea, cough, chest pain

Grade 3 or 4

  • Severe new symptoms
  • New or worsening hypoxia
  • Life threatening
  • Difficulty in breathing, ARDS

Management escalation pathway

  • Consider delay of treatment
  • Monitor Symptoms every 2-3 weeks
  • When worsening: treat as grade 2 or 3-4

Assessment and Investigations

  • Chest X-Ray
  • Regular blood analysis including CRP
  • Consider sputum sample and screening for viral, opportunistic or specific bacterial infections (mycoplasma, legionella) depending on the clinical contact

Management escalation pathway

  • Withhold ICPi

  • Monitor symptoms daily: hospitalize patient
  • Start antibiotic if suspicion of infection (fever, CRP, neutrophil counts, purulent sputa)
  • If no evidence of infection or no improvement with antibiotics after 48h add (methyl)prednisolone 1 mg/kg/day orally
  • If no improvement after 48h of oral prednisolone, manage as per Grade 3
  • Consider Pneumocystis prophylaxis depending on the clinical context (especially in immunosuppressed patients)

Assessment and Investigations

  • High resolution CT
  • Regular blood analysis including CRP
  • Analyse sputum sample (incl screening for viral, opportunistic or specific bacterial infections (mycoplasma, legionella))
  • Discuss bronchoscopy and BAL with pneumologist
  • Perform lung function tests, including TCLO

Management escalation pathway

  • Discontinue ICPi
  • Hospitalize patient, consider ICU care
  • Start (methyl)prednisolone i.v. 2 mg/kg/day + cover with empiric antibiotics
  • consider treatment with cotrimoxazole for Pneumocystis

Assessment and investigations

  • Perform blood test
  • Analyze sputum for bacteria, viral and other opportunistic infections
  • High resolution CT
  • Bronchoscopy and BAL as well as lung function tests to be discussed with pneumologist

If no improvement or worsening after 48h

  • Discuss addition of Infliximab 5 mg/kg or other secondary immunosuppressant with pneumologist or in multidisciplinary board
  • Continue with i.v. steroids
  • Exclude other diagnosis including diaphragm paralysis due to concurrent immune related (cardio)myositis


Check in medical history

  • Underlying cardiac or respiratory disease: pulmonary hypertension, connective tissue disease (eg preexisting interstitial lung disease)
  • Past or ongoing infectious diseases: HIV, Influenza, Mycobacterium Tuberculosis exposure
  • Smoking, travel and allergens history (including exposure to home occupational aeroallergens)

Differential Diagnosis

  • other causes of pneumonia (including atypical pneumonia, Pneumocystis, Tuberculosis, …)
  • Carcinomatous lymphangitis
  • Pulmonary oedema
  • Pulmonary emboli
  • Sarcoidosis

Steroid weaning upon symptom control

  • Grade 2: wean oral steroids over at least 6 weeks, titrate to symptoms
  • Grade 3/4: wean steroids over at least 8 weeks

Caution during steroid treatment:

  • Calcium & vitamin D supplementation as per local guidelines
  • Pneumocystis prophylaxis to be considered: Cotrimoxazol 480mg bi-daily 3 times a week

Restart immunotherapy

  • Should be discussed multidisciplinary among oncologist and pneumologist  patient should be included in risk assessment (only 7 out 10 cases of pneumonitis had a relaps of pneumonitis upon ICPI restart
  • Only indicated once steroids are completely weaned and CT lung is completely cleared


ICPi: Immune Checkpoint Blockade Inhibition
ARDS: Acute Respiratory Distress Syndrome
CRP: C Reactive Protein
ULN: Upper Limit of Normal
TFT: Thyroid Function Test
TCLO: Transfer Factor for Carbon Monoxide
MMF: Mycophenolate mofetil