Abstract Introduction Pembrolizumab is an immune-checkpoint inhibitor that acts on the PD-1 receptor to increase the cell-mediated immune response against various solid and hematologic malignancies. As of 2024, over 2 million patients have taken pembrolizumab, with any-grade pneumonitis reported in 5.9% of patients and severe (grade 3-5) pneumonitis reported in 2.6%. Case Report An 80-year-old male with a history of stage IV melanoma presented to the emergency department with four days of dry cough and dyspnea. He was hypoxemic with an oxygen saturation of 80% on room air and required supplemental oxygen to maintain saturations above 92%. Notably, he had received his first dose of pembrolizumab 13 days prior to symptom onset. A CT scan of the chest on admission revealed dense consolidations in the lower lobes, diffuse band-like fibrosis in the middle and upper lung fields, and diffuse ground-glass opacities, concerning for grade III pneumonitis. He was admitted for acute hypoxemic respiratory failure secondary to presumed community-acquired pneumonia. He was initially started on ceftriaxone and azithromycin without clinical improvement, and a broad infectious workup, including sputum culture and viral PCR panel, was negative. His respiratory status decompensated, and he required high-flow oxygen therapy by nasal cannula with an FiO2 of 100%. Repeat CT of the chest revealed worsening fibrosis as well as the development of diffuse traction bronchiectasis, concerning for acute interstitial pneumonitis (AIP) (Figure 1). He was treated with pulse-dosed methylprednisolone, leading to gradual improvement, and was continued on a lengthy steroid taper. Discussion The patient’s presentation of cough and respiratory failure with consolidations on imaging was initially concerning for community-acquired pneumonia versus opportunistic infection due to his immunosuppression. However, his negative infectious workup and lack of response to antibiotics made this unlikely. He had no prior history of lung disease, radiation therapy to the chest, or exposure to inhaled particles known to cause pneumoconioses, ruling out chronic etiologies. His improvement with pulse-dose steroids raised suspicion for pembrolizumab-induced AIP given the acuity of decompensation and rapid development of worsening fibrosis and traction bronchiectasis. This case demonstrates a concern for pembrolizumab-induced AIP following a single dose of the immune-checkpoint inhibitor therapy, an adverse effect which carries significant morbidity and mortality. While previous case studies report these adverse autoimmune or inflammatory effects after multiple doses, this vignette highlights a novel presentation after one dose, emphasizing that there need not be long-term exposure to the treatment before lung adverse events begin. This abstract is funded by: None
Shaughnessy et al. (Fri,) studied this question.