How should fleeting pulmonary infiltrates be managed in a patient receiving chemotherapy with dostarlimab (Jemperli)?

Management of Fleeting Pulmonary Infiltrates in Patients Receiving Dostarlimab

Fleeting pulmonary infiltrates in a patient on dostarlimab should be presumed to be immune-related pneumonitis until proven otherwise, requiring immediate high-resolution chest CT, exclusion of infection, and prompt initiation of corticosteroids for grade ≥2 disease with temporary or permanent discontinuation of dostarlimab depending on severity.

Initial Diagnostic Approach

When fleeting infiltrates appear on imaging in a dostarlimab-treated patient, you must rapidly differentiate immune-related pneumonitis from other causes:

• Obtain high-resolution chest CT with contrast immediately to characterize the pattern and exclude tumor progression, pulmonary embolism, or pleural disease 1
• Rule out infection aggressively: obtain sputum, blood, and urine cultures; consider bronchoalveolar lavage (BAL) to exclude infectious pneumonia or tumor infiltration 1
• Exclude cardiac causes: assess for heart failure, myocarditis, acute myocardial infarction, and arrhythmias 1

The FDA label for dostarlimab (Jemperli) reports immune-mediated pneumonitis in 2.3% of patients, with Grade 2 (1.3%), Grade 3 (0.8%), and Grade 4 (0.2%) cases 2. Pneumonitis led to permanent discontinuation in 1.3% of patients and was fatal in some cases 2.

CT Pattern Recognition

The Fleischner Society guidelines emphasize that CT patterns correlate with severity and guide management 3:

• Organizing pneumonia (OP) pattern (most common, 23%): patchy consolidation and ground-glass opacities
• Hypersensitivity pneumonitis (HP) pattern (16%): ground-glass opacities with small nodular lesions
• Diffuse alveolar damage (DAD) pattern: diffuse ground-glass opacity, highest toxicity grade, worst prognosis
• NSIP pattern: lower toxicity grades

Critical pitfall: DAD pattern carries the highest mortality risk and requires immediate aggressive intervention 3.

Grade-Based Management Algorithm

Grade 1 (Asymptomatic or Mild Symptoms)

• Continue dostarlimab with close monitoring
• Repeat imaging in 3-5 days
• No corticosteroids required initially

Grade 2 (Moderate Symptoms: Dyspnea with Activity)

• Withhold dostarlimab immediately 2
• Initiate prednisone 1 mg/kg/day (or equivalent) 1
• Taper corticosteroids over 4-6 weeks after improvement to grade <1 1
• Rechallenge with dostarlimab only upon complete resolution and on an individual basis with intensive monitoring 1
• 79% of dostarlimab pneumonitis cases required systemic corticosteroids 2

Grade 3-4 (Severe: Dyspnea at Rest, Life-Threatening)

• Permanently discontinue dostarlimab 2
• Initiate methylprednisolone 1-2 mg/kg/day IV (or equivalent) 1
• Taper over 6-8 weeks after improvement to grade <1 1
• If no improvement within 72 hours: escalate immunosuppression with:
  • Tocilizumab 8 mg/kg (one dose, repeat every 2 weeks if needed), OR
  • Infliximab 5 mg/kg (one dose, repeat every 2 weeks if needed), OR
  • IVIG 2 g/kg over 2-5 days
  • Alternative agents: mycophenolate mofetil 1 g twice daily or cyclophosphamide 1

Important caveat: In the dostarlimab clinical experience, 5 patients reinitiated therapy after pneumonitis; 2 of these (40%) had recurrence 2. This high recurrence rate argues strongly against rechallenge in grade 3-4 cases.

Special Considerations

Risk Factors for Severe Pneumonitis

Monitor more aggressively in patients with:

• Prior thoracic radiation (6.0% incidence vs 3.8% overall) 3
• Pre-existing interstitial lung disease or COPD (5.3% incidence) 3
• Male sex, smoking history 3
• Age ≥55 years 3

Mandatory: Discuss cases with pre-existing ILD with a pulmonologist before initiating dostarlimab 1.

Timing and Monitoring

• Median onset of ICI-related pneumonitis: 2.1 months in lung cancer patients 3
• Pneumonitis can occur at any time during treatment or even after discontinuation 2
• Baseline pulmonary function tests and chest imaging are essential before starting therapy 1

Distinguishing from Other Causes

The "fleeting" nature suggests either:

1. Organizing pneumonia pattern (most likely with ICIs, responds well to steroids)
2. Cryptogenic organizing pneumonia-like reaction (migratory infiltrates)
3. Infection (must be excluded first)

One case report describes a focal lobar infiltrate with PD-1 inhibitors that resolved completely with drug cessation and prednisone without antibiotics 4, demonstrating that atypical patterns can occur.

Rare but Critical Differential

A recent case report documented pulmonary-renal syndrome with dostarlimab (necrotizing crescentic glomerulonephritis with massive intra-alveolar hemorrhage) 5. If systemic symptoms or renal dysfunction accompany pulmonary infiltrates, check:

• Creatinine, urinalysis
• ANCA, ANA
• Consider broader autoimmune workup

Outcome Data

From dostarlimab clinical trials 2:

• Pneumonitis resolved in 11 of 14 patients (79%)
• 9 patients had dostarlimab withheld
• Of 5 who reinitiated therapy, 2 had recurrence (40% recurrence rate)

The high recurrence rate and potential for fatal outcomes mandate a conservative approach to rechallenge, particularly in grade 3-4 cases.