Pneumonitis – Grade 3 or 4

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 (until PCR comes out negative)

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)
  • Discuss previous exposure to thoracic radiotherapy with radiotherapist

Differential Diagnosis

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

Steroid considerations

  • Grade 2: wean oral steroids over at least 6 weeks, titrate to symptoms
  • Grade 3/4: wean steroids over at least 8 weeks (evaluate with CT scan)

Caution during steroid treatment:

  • Calcium & vitamin D supplementation as per local guidelines
  • Pneumocystis prophylaxis to be considered: Cotrimoxazol 480mg 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