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