Study Characterizes Pneumonitis Risk With Immunotherapeutic Agents

Pneumonitis occurs in approximately 5% of cancer patients treated with anti–programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy agents, according to a new analysis. The complication tends to be low grade and easily resolved, though it can worsen and result in death in rare cases.

“One of the remarkable characteristics of anti–PD-1/PD-L1 monoclonal antibodies is their relatively mild toxicity profile,” wrote study authors led by Matthew D. Hellmann, MD, of Memorial Sloan Kettering Cancer Center in New York. “However, immune-related adverse events can occur and may be severe.” Pneumonitis is one such immune-related adverse event, and it accounted for several deaths in early trials of these agents.

The new study included 915 patients who received nivolumab, pembrolizumab, atezolizumab, or several other similar agents either alone or in combination with an anti–cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) agent for a variety of cancers; 578 of them were treated at Memorial Sloan Kettering, and another 337 were treated for melanoma only at the Melanoma Institute Australia. The results were published in the Journal of Clinical Oncology.

The overall incidence of pneumonitis was 5%, occurring in 43 patients. That rate was similar at both institutions, with 27 cases in New York and 16 cases in Australia. The incidence was higher among those who received combination therapy than in those receiving monotherapy (10% vs 3%; P < .01). There was no difference between PD-1 and PD-L1 antibodies.

Pneumonitis occurred across several malignancies, including melanoma, non–small-cell lung cancer, bladder carcinoma, and others. The median time to onset of the complication was 2.8 months, though it ranged widely from 9 days to more than 19 months. The onset was earlier in combination therapy patients. Most commonly, patients presented with pneumonitis with dyspnea and cough, with fever and chest pain less commonly seen.

Most of the cases were grade 1 or 2 pneumonitis, and most were treated as outpatients; most of those resolved with drug holding and/or corticosteroid therapy. The issue improved or resolved in 86% of all cases, and 5 patients (12%) clinically worsened during pneumonitis treatment. Those five patients were treated with additional immunosuppression beyond corticosteroids; all ultimately died. Most of those deaths were multifactorial in cause, though the authors noted that one could be firmly attributed to pneumonitis.

“Pneumonitis is an uncommon but potentially serious toxicity that occurs in 5% of patients who receive anti–PD-1/PD-L1 antibodies,” the authors concluded. “Treating physicians should be aware of its diverse clinical, radiologic, and pathologic features and that it may develop at any time during a patient’s treatment course.” They added that further study is needed to better understand the biology of pneumonitis and subsequently optimize its management.