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Management guidelines for pulmonary irAEs

Common pulmonary irAE symptoms

Radiographic changes
New or worsening cough
Shortness of breath
Chest pain
Hypoxia

International guideline (ASCO, ESMO and NCCN) recommendations for pulmonary irAEs1-3 ^

^ For detailed guidelines, please refer to original publication

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NCCN1 ESMO2 ASCO3
Grade 1  Consider holding immunotherapy Consider delaying immunotherapy

If symptoms worsen, treat as grade 2		 Consider holding immunotherapy

If no improvement, treat as Grade 2
Grade 2 Hold immunotherapy
Consider empiric antibiotics if infection is suspected
Prednisone/IV methylprednisolone 1–2 mg/kg/day* Oral prednisolone 1 mg/kg/day* Prednisone 1–2 mg/kg/day and taper over 4–6 weeks*
If no improvement after 48–72 hours of recommended corticosteroids, treat as Grade 3

Consider pulmonary consultation 		If no improvement after 48 hours of recommended corticosteroids, treat as Grade 3

Consider pneumocystis prophylaxis 		If no improvement after 48–72 hours of recommended corticosteroids, treat as Grade 3

Consider pulmonary and infectious disease consultation
Grade 3/4 Discontinue immunotherapy
Consider empiric antibiotics
Methylprednisolone IV 1–2 mg/kg/day*
If no improvement, consider infliximab, IVIG, MMF, cyclophosphamide
Hospitalise
Consult pulmonary and infectious disease   - Consult pulmonary and infectious disease

*Consult ‘Steroid and immunosuppressor usage’ table for more information

ASCO, American Society of Clinical Oncology; ESMO, European Society for Medical Oncology; IV, intravenous; IVIG, intravenous immunoglobulin; MMF, mycophenolate mofetil; NCCN, National Comprehensive Cancer Network.

Diagnostic assessment may include chest x-ray, CT, pulse oximetry, blood panels (FBC/UEC/LFTs/TFTs/Ca/ESR/CRP),2 nasal swabs, sputum and urine testing.1-3 ESMO recommends considering a sputum sample and screening for infectious causes even at the Grade 1 level2; ASCO and the NCCN recommend these investigations only at Grade ≥2.1,3

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NCCN, ESMO, ASCO1-3
Grade 1 Grade 2 Grade 3 Grade 4
Asymptomatic, confined to one lobe or <25% of lung parenchyma.1-3

Clinical or diagnostic observations only.3 		Symptomatic, involving more than one lobe of the lung or 25–50% of the lung parenchyma; medical intervention indicated; limiting instrumental ADL.3

The presence of new or worsening symptoms.1,2

Dyspnoea, shortness of breath, cough, chest pain, increased oxygen requirement.2



Consider cardiac etiologies.1 		Severe (new) symptoms.1-3

Involves all lung lobes or >50% of lung parenchyma, limiting self-care ADL, new/worsening hypoxia, oxygen indicated.1,3

Difficulty in breathing, acute respiratory distress.2 		As Grade 3, with life-threatening respiratory compromise1-3.

Urgent intervention (intubation) indicated.3

ADL, activities of daily living; ASCO, American Society of Clinical Oncology; Ca, calcium; CRP, C-reactive protein; CT, computed tomography; ESMO, European Society for Medical Oncology; ESR, erythrocyte sedimentation rate; FBC, full blood count; LFT, liver function test; NCCN, National Comprehensive Cancer Network; TFT, thyroid function test; UEC, urea, electrolytes, creatinine.

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  NCCN1 ESMO2 ASCO3
Grade 1 Reassess history, conduct a physical examination and pulse oximetry on the schedule indicated below, plus any supplementary investigations as described.
Within 1–2 weeks.  

Consider a chest CT with contrast, and repeat CT in 4–6 weeks or if clinically indicated by patient developing symptoms.

 Every 2–3 days.  

Baseline indications:

  • Chest CT with contrast (consider repeating chest CT if clinical deterioration)
  • Pulse oximetry
  • Blood tests

Consider sputum and screening for viral, opportunistic or specific bacterials infections (Mycoplasma, Legionella) depending on the clinical context.

 Weekly.  

May offer chest x-ray. May offer repeat CT in 3–4 weeks as well as repeat spirometry/DLCO if done at baseline.
Grade 2 Every 3–7 days with H&P and pulse oximetry.

Consider chest CT with contrast and repeat chest CT in 3–4 weeks.

Consider infectious workup (nasal swab, sputum culture, blood culture, urine antigen test).

Consider bronchoscopy with BAL and consider transbronchial lung biopsy if clinically feasible.

 Daily.  

Outpatient monitoring: Chest CT with contrast, consider infection work (sputum, blood and urine culture);consider bronchoscopy with BAL to rule out infection and tumour infiltration.


Baseline indications: as grade 1, with the addition of repeating chest x-ray weekly, baseline blood tests and LFTs including TLCO.

 At least once per week.

Consider bronchoscopy with BAL ± transbronchial biopsy
Grade 3–4 At these grades, patients should be admitted for inpatient care/hospitalised and receiving active medical intervention. If feasible, continue to conduct tests as recommended above.

ASCO, American Society of Clinical Oncology; BAL, bronchoalveolar lavage; CT, computed tomography; DLCO, diffusing capacity of lung for carbon monoxide; ESMO, European Society for Medical Oncology; LFT, liver function test; NCCN, National Comprehensive Cancer Network; TCLO, transfer factor for carbon monoxide.

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  NCCN1 ESMO2 ASCO3
Grade 2 Prednisone/methylprednisolone 1–2 mg/kg/day until symptoms improve to Grade 1, then taper over 4–6 weeks. If no evidence of infection or no improvement after 48 hours of antibiotics:  

oral prednisolone 1 mg/kg/day, wean over 4–6 weeks once improved to baseline.

 Prednisone 1–2 mg/kg/day, tapering over 4–6 weeks.*
Grade 3–4 Methylprednisolone 1–2 mg/kg/day, assess response within 48 hours

If no improvement in 48 hours, may add:  
  • IVIG, total dosing 2 g/kg administered in daily divided doses over 2-5 days or per package insert
  • MMF 1–1.5g BID, tapering in consultation with pulmonary service
  • Alternative options:
    • Tocilizumab
    • Infliximab, 5 mg/kg, consider second dose after 14 days

Plan corticosteroid tapering over ≥6 weeks.

 (methyl)prednisolone IV 1–2 mg/kg/day

If no improvement in 48 hours, may add:  
  • Tocilizumab 8mg/kg or
  • Infliximab 5mg/kg ± IVIG

Consider MMF or cyclophosphamide.
Wean corticosteroids over at least 6–8 weeks once improved to baseline.†

 (methyl)prednisolone IV 1–2 mg/kg/day

If no improvement in 48 hours, may add:  
  • Infliximab IV
  • Mycophenolate mofetil 0.5–1 g PO
  • IVIG 2 g/kg over 2–5 days in divided doses of 400–500 mg/kg
  • Cyclophosphamide 1–2 mg/kg/day

Taper corticosteroids over 4–6 weeks.*

*Subset of patients may develop chronic pneumonitis and may require longer taper. Chronic pneumonitis is a described phenomenon where the incidence is not known but <2%.3
†Supplement calcium and vitamin D as per local guidelines; For pneumocystis prophylaxis use cotrimoxazole 480 mg BID on Monday, Wednesday and Friday or inhaled pentamidine if cotrimoxazole allergy is present.2

ASCO, American Society of Clinical Oncology; BID, twice daily; ESMO, European Society for Medical Oncology; IV, intravenous; IVIG, intravenous immunoglobulin; MMF, mycophenolate mofetil; NCCN, National Comprehensive Cancer Network; PO, orally.

References:

  1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Management of immunotherapy-Related Toxicities. Version 1.2025. Available at: https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf. Accessed March 2025.
  2. Haanen J, et al.  Ann Oncol 2022;33:1217–1238. Available at: https://www.annalsofoncology.org/article/S0923-7534(22)04187-4/fulltext. Accessed March 2025.
  3. Schneider BJ, et al.  J Clin Oncol 2021;39:4073–4126. Available at: https://ascopubs.org/doi/full/10.1200/JCO.21.01440. Accessed March 2025.
  4. OPDIVO® (nivolumab) Product Information, BMS Hong Kong.
  5. YERVOY® (ipilumab) Product Information, BMS Hong Kong.
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