Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy

Area of Science:

• Oncology
• Immunology
• Pulmonology

Background:

• Pneumonitis is an uncommon but potentially fatal toxicity associated with anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) monoclonal antibodies (mAbs).
• The clinical, radiologic, and pathologic features of this toxicity are not well-described.
• Understanding these features is crucial for managing patients receiving these novel immunotherapies.

Purpose of the Study:

• To describe the clinical, radiologic, and pathologic features of pneumonitis associated with anti-PD-1/PD-L1 mAb therapy.
• To determine the incidence of pneumonitis in patients receiving monotherapy versus combination therapy.
• To examine the outcomes of pneumonitis in patients treated with these agents.

Main Methods:

• Retrospective review of patients who received anti-PD-1/PD-L1 mAbs at two institutions.
• Pneumonitis diagnosis by treating investigator, excluding malignant lung infiltration or infection.
• Analysis of clinical, radiologic, and pathologic features, and associations with therapy and outcomes.

Main Results:

• Pneumonitis occurred in 5% of 915 patients, with similar incidence in melanoma and non-small cell lung cancer.
• Incidence was significantly higher with combination immunotherapy (10%) versus monotherapy (3%) (P < .01).
• Most cases (72%) were low grade and improved with treatment; however, 5 patients died due to pneumonitis or related complications.

Conclusions:

• Pneumonitis from anti-PD-1/PD-L1 mAbs is a toxicity with variable presentation and onset.
• Combination immunotherapy with anti-cytotoxic T-cell lymphocyte-4 mAb increases pneumonitis risk.
• While most cases are manageable, severe outcomes including death can occur, necessitating careful monitoring and management.