Table 3.

Management of Lung irAEs in Patients Treated With ICPis

3.0 Lung Toxicities
3.1 Pneumonitis
Definition: Focal or diffuse inflammation of the lung parenchyma (typically identified on CT imaging)
No symptomatic, pathologic, or radiographic features are pathognomonic for pneumonitis
Diagnostic work-up
Should include the following: CXR, CT, pulse oximetry
For G2 or higher, may include the following infectious work-up: nasal swab, sputum culture and sensitivity, blood culture and sensitivity, urine culture and sensitivity
Grading	Management
G1: Asymptomatic, confined to one lobe of the lung or < 25% of lung parenchyma, clinical or diagnostic observations only	Hold ICPi with radiographic evidence of pneumonitis progression  May offer one repeat CT in 3–4 weeks; in patients who have had baseline testing, may offer a repeat spirometry/DLCO in 3–4 weeks  May resume ICPi with radiographic evidence ofimprovement or resolution.  If no improvement, should treat as G2  Monitor patients weekly with history and physical examination and pulse oximetry; may also offer CXR
G2: Symptomatic, involves more than one lobe of the lung or 25%–50% of lung parenchyma, medical intervention indicated, limiting instrumental ADL	Hold ICPi until resolution to G1 or less  Prednisone 1–2 mg/kg/d and taper by 5–10 mg/wk over 4–6 weeks  Consider bronchoscopy with BAL  Consider empirical antibiotics  Monitor every 3 days with history and physical examination and pulse oximetry, consider CXR; no clinical improvement after 48–72 hours of prednisone, treat as G3
G3: Severe symptoms, hospitalization required, involves all lung lobes or > 50% of lung parenchyma, limiting self-care ADL, oxygen indicated G4: Life-threatening respiratory compromise, urgent intervention indicated (intubation)	Permanently discontinue ICPi  Empirical antibiotics; (methyl)prednisolone IV 1–2 mg/kg/d; no improvement after 48 hours, may add infliximab 5 mg/kg or mycophenolate mofetil IV 1 g twice a day or IVIG for 5 days or cyclophosphamide; taper corticosteroids over 4–6 weeks  Pulmonary and infectious disease consults if necessary  Bronchoscopy with BAL ± transbronchial biopsy  Patients should be hospitalized for further management
Additional considerations  GI and Pneumocystis prophylaxis with PPI and Bactrim may be offered to patients on prolonged corticosteroid use (> 12 weeks), according to institutional guidelines34–37  Consider calcium and vitamin D supplementation with prolonged corticosteroid use  The role of prophylactic fluconazole with prolonged corticosteroid use (> 12 weeks) remains unclear, and physicians should proceed according to institutional guidelines33  Bronchoscopy + biopsy; if clinical picture is consistent with pneumonitis, no need for biopsy
All recommendations are expert consensus based, with benefits outweighing harms, and strength of recommendations are moderate.

Abbreviations: ADL, activities of daily living; BAL, bronchoalveolar lavage; CT, computed tomography; CXR, chest x-ray; DLCO, diffusing capacity of lung for carbon monoxide; G, grade; ICPi, immune checkpoint inhibitor; irAE, immune-related adverse event; IV, intravenous; IVIG, intravenous immunoglobulin; PPI, proton pump inhibitor.