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Pneumonitis

It is important to note that pneumonitis secondary to immunotherapy is a toxicity of variable onset as well as variable clinical, radiological and pathological appearances.

  • Most commonly occurs in patients on anti PD-1 or anti PDL-1 therapy, but rarely in patients on anti CTLA-4 monotherapy.
  • It is more common in patients on combination anti PD-1 and anti CTLA-4 therapy, e.g. nivolumab and ipilimumab.
  • Pneumonitis occurs in 2-4% of patients on immunotherapy.
  • Clinical symptoms can include: SOB (40-50%), cough (35%), fever, chest pain
  • It can rapidly progress, leading to respiratory failure.
  • The onset of immunotherapy-related pneumonitis is variable and can range from 2-24 months; the median onset is 3 months.
  • Radiological features of pneumonitis are not pathognomonic, and can include ground glass opacities, a cryptogenic organising pneumonia-like appearance and interstitial pneumonia pattern as well as characteristics of hypersensitivity pneumonitis.

Questions

  • What treatment is the patient on and when was it last administered?
  • Is the patient on a clinical trial? If so, which trial and are they still taking any oral trial medication?
  • Are they short of breath, or is there worsening shortness of breath from baseline?
  • Do they have a fever? Do they have a cough? Characteristics of the cough?
  • Does the patient suffer from any chronic respiratory disease (COPD, asthma, bronchitis, pulmonary hypertension, connective tissue disorders)?
  • Are they on any other regular medication?
  • Have they had any radiotherapy to the chest?
  • Have they had any exposure to influenza or mycobacterium?
  • Smoking history
  • Travel history
  • Allergy history including exposure to home/occupational allergens

Grade 1 (Green)

Asymptomatic,

Incidental interstitial changes on CT suggesting an ILD

Advice

Monitor symptoms every 2-3 days

Baseline investigations

Non contrast HRCT

Consider delay IO

Discuss with respiratory for Bronchoscopy

If symptoms develop or worsen then treat as grade 2 or 3-4

Grade 2 (Amber)

Patient has cough or breathlessness but not needing oxygen

Advice

Needs clinical review in A&E or AOCU

Monitor symptoms daily

Baseline investigations

Non contrast HRCT

Withhold immunotherapy Bronchoscopy

Grade 3 (Red)

Severe new symptoms including cough, dyspnoea, chest pain, new/worsening hypoxia, respiratory failure needing oxygen, life threatening, ARDS

Advice

Will need urgent admission to hospital

Monitor symptoms

Baseline investigations

HRCT, Urgent respiratory review for bronchoscopy and BAL  (if sats  >92% on up to 2 litres/min O2)

Discontinue Immunotherapy

Grade 4 (Red)

Severe new symptoms including cough, dyspnoea, chest pain, new/worsening hypoxia, respiratory failure needing oxygen, life threatening, ARDS

Advice

Will need urgent admission to hospital

Monitor symptoms

Baseline investigations

HRCT, Urgent respiratory review for bronchoscopy and BAL  (if sats  >92% on up to 2 litres/min O2)

Discontinue Immunotherapy

Handover management with patient’s team, discuss all interruptions of treatment with team +/- AOS prior to proceeding. Arrange follow up review as necessary.


Initial assessment – patient seen in AOCU

Clinical assessment and examination including observations

Symptoms SOB, chest pain, cough, increased oxygen requirements

Baseline investigations: Covid Swab

-Bloods FBC, U&Es, LFTs, bone profile, TFTs, ESR, CRP, LDH, Creatinine Kinase, ACE, ANA, myositis antibodies, BNP

-Atypical screen: Legionella and mycoplasma, pneumococcus, chlamydia pneumophilia

-Sputum sample for viral (Extended viral respiratory PCR), bacterial and opportunistic infections (Beta-D glucan)

-Blood and urine culture

CXR and Non contrast high-resolution CT (HRCT), if PE suspected then CTPA

Refer to Respiratory medicine – Bronchoscopy and BAL (infection, tumour infiltration)

Refer all cases at presentation of any grade to Dr Raminder Aul Raminder.Aul@stgeorges.nhs.uk


Management

  • Discontinue immunotherapy if Grade 2 or above
  • If Grade 2: Start antibiotics as per hospital policy if concerned about infection (raised CRP/WCC, fever, septic). If no improvement on antibiotics after 48 hours or no evidence of infection: Bronchoscopy and after Start intravenous Methylprednisolone 10mg/kg/day x 3 (500/750/1000mg). followed by oral prednisolone 10mg x d for at least 6 weeks – repeat HRCT at 4-6 weeks
  • If no improvement after 48 hours of oral steroids then manage as grade 3. If improvement after 48 hours, then Weekly Follow up: CXR, bloods and lung function tests including TLCO and wean off over 4-6 weeks, titrate to symptoms. Respiratory FU if needed
  • Grade 3/4: IV Methylprednisolone as in Grade 2 followed by oral prednisolone starting at 0.5mg/kg/d and taper off. Cover with empiric antibiotics as well as discussion about escalation and ventilation. Early ITU and respiratory review should be considered with discussion about bronchoscopy and BAL.
  • If no improvement or worsening after 48 hours, then discuss urgently with Respiratory to consider cyclophosphamide or other biologics – Infliximab or mycophenolate (only after discussion with consultant oncologist)

    Continue with steroids and wean as clinically indicated over 4-6 w.

    CT in 6 weeks and respiratory follow up