Immune-Related Pneumonitis: Recognition and Management Guide

Immune-related pneumonitis is a potentially serious lung inflammation caused by checkpoint inhibitors like Keytruda, OPDIVO, and Tecentriq. While it affects only 3-5% of patients, early recognition and treatment are critical to prevent serious complications.

**What Is Immune-Related Pneumonitis?**

Pneumonitis is inflammation of lung tissue caused by an overactive immune response to checkpoint inhibitor therapy. Unlike infection (pneumonia), it's a sterile inflammation that requires immune suppression rather than antibiotics.

Types of pneumonitis patterns:
- Cryptogenic organizing pneumonia (most common)
- Nonspecific interstitial pneumonia
- Hypersensitivity pneumonitis
- Acute interstitial pneumonia (rare, severe)

**Risk Factors**

Higher Risk:
- Combination immunotherapy (OPDIVO + Yervoy: 7-10% risk)
- History of lung disease (COPD, asthma, prior radiation)
- Lung cancer diagnosis
- Prior thoracic radiation
- Smoking history
- Asian ethnicity (higher incidence reported)

Lower Risk:
- Single-agent PD-1/PD-L1 inhibitor (2-4%)
- No pre-existing lung disease
- Melanoma or kidney cancer diagnosis

**Recognizing Symptoms**

Early Symptoms (Grade 1-2):
- New or worsening dry cough
- Mild shortness of breath with exertion
- Decreased exercise tolerance
- Chest tightness or discomfort
- Low-grade fever

Severe Symptoms (Grade 3-4):
- Shortness of breath at rest
- Rapid breathing (>20 breaths/minute)
- Oxygen saturation <90%
- Severe cough
- Chest pain
- High fever
- Confusion

**When to Seek Immediate Medical Attention**

Go to ER immediately if:
- Severe shortness of breath
- Blue lips or fingernails
- Chest pain
- Oxygen saturation <92% on home oximeter
- Confusion or altered mental status
- Unable to complete sentences due to breathlessness

Contact your oncology team same-day if:
- New persistent cough
- Mild dyspnea with activity
- Low-grade fever
- Decreased exercise tolerance

**Diagnostic Workup**

Physical Examination:
- Lung sounds (crackles or wheezing)
- Oxygen saturation
- Respiratory rate and effort
- Vital signs

Imaging:
- Chest X-ray (initial screening)
- High-resolution CT chest (definitive imaging)
- Patterns seen: Ground-glass opacities, consolidation, interstitial infiltrates

Laboratory Tests:
- Complete blood count
- Comprehensive metabolic panel
- Inflammatory markers (CRP, ESR)
- Arterial blood gas if severe
- Infectious workup (rule out pneumonia)

Additional Tests:
- Pulmonary function tests
- Bronchoscopy with bronchoalveolar lavage (if diagnosis unclear)
- Lung biopsy (rarely needed)

**Treatment by Severity**

Grade 1 (Mild, Asymptomatic):
- Hold immunotherapy temporarily
- Close monitoring (imaging every 3-7 days)
- Consider low-dose steroids if not improving
- Resume immunotherapy only if resolved

Grade 2 (Moderate Symptoms):
- Hold immunotherapy
- Prednisone 1 mg/kg daily (60-80 mg typical)
- Daily monitoring initially
- Repeat CT in 3-7 days
- Taper steroids over 4-8 weeks once improved
- Consider permanent discontinuation of immunotherapy

Grade 3-4 (Severe or Life-Threatening):
- Permanently discontinue immunotherapy
- Hospitalization required
- High-dose IV methylprednisolone 2-4 mg/kg daily
- Oxygen support (may need mechanical ventilation)
- Additional immunosuppression if steroid-refractory:
* Infliximab 5 mg/kg IV
* Mycophenolate mofetil
* Cyclophosphamide (severe cases)
* IVIG (intravenous immunoglobulin)

**Steroid Tapering Protocol**

Initial High Dose (1-2 weeks):
- 1-2 mg/kg prednisone equivalent
- Monitor for improvement

Gradual Taper (6-12 weeks total):
- Reduce by 10 mg every 1-2 weeks until 30 mg
- Then reduce by 5 mg every 1-2 weeks until 10 mg
- Final taper: 2.5 mg decrements over several weeks

Monitoring During Taper:
- Symptoms should not worsen
- Repeat chest CT at key milestones
- Watch for steroid side effects
- Be alert for pneumonitis recurrence

**Monitoring and Follow-Up**

During Active Pneumonitis:
- Daily symptom assessment
- Pulse oximetry (home monitor)
- Weekly labs initially
- Chest imaging as clinically indicated

After Resolution:
- Baseline CT before any immunotherapy resumption
- Regular surveillance imaging
- Long-term pulmonary function monitoring
- Watch for late recurrence (can occur months later)

**Resuming Immunotherapy**

Generally NOT recommended if:
- Grade 3-4 pneumonitis
- Required high-dose steroids
- Steroid-refractory disease
- Recurrent pneumonitis

May consider rechallenge if:
- Grade 1-2 pneumonitis
- Completely resolved
- Cancer progressing without treatment
- No alternative therapies available
- Patient fully informed of risks

Rechallenge Protocol:
- Complete resolution documented by CT
- Off steroids for ≥4 weeks
- Close monitoring after resumption
- Lower dose or longer interval may reduce risk

**Living with Lung Damage**

Some patients develop permanent lung changes:
- Residual fibrosis on CT scans
- Chronic cough
- Exercise intolerance
- Oxygen requirement (rare)

Management Strategies:
- Pulmonary rehabilitation
- Supplemental oxygen if needed
- Cough suppressants
- Breathing exercises
- Avoid respiratory irritants (smoke, pollution)
- Annual flu and pneumonia vaccines

**Prevention Strategies**

Baseline Assessment:
- Chest CT before starting immunotherapy
- Pulmonary function tests if lung disease history
- Patient education about symptoms

During Treatment:
- Regular symptom inquiries at each visit
- Low threshold for chest imaging if symptoms
- Avoid other lung irritants
- Home pulse oximeter for high-risk patients

**Questions to Ask Your Doctor**

- What's my personal risk of developing pneumonitis?
- What symptoms should I watch for?
- Should I have a baseline chest CT?
- Do I need a home pulse oximeter?
- If pneumonitis occurs, can I ever resume immunotherapy?
- Are there alternative treatments for my cancer?

**Patient Success Story**

"After my 6th OPDIVO infusion, I developed a dry cough and mild shortness of breath. My oncologist immediately ordered a CT scan showing early pneumonitis. We stopped OPDIVO and started prednisone 60 mg daily. Within a week, I felt better. After an 8-week steroid taper, my CT normalized. Although I couldn't resume OPDIVO, my cancer remained stable for 14 months. Early detection made all the difference."

Our team can provide resources for managing immunotherapy-related lung complications and connect you with pulmonary specialists experienced in these conditions.