Abstract Introduction Durvalumab, a PD-L1 inhibitor used as consolidation therapy for stage III non-small cell lung cancer (NSCLC), has been associated with severe immune-related pneumonitis as a treatment-related side effect. While Checkpoint inhibitor pneumonitis (CIP) is primarily considered an autoimmune-mediated toxicity, infectious factors may amplify pulmonary inflammation and alter disease severity. We report a case of grade 4 durvalumab induced pneumonitis associated with concurrent Pneumocystis jirovecii infection (PJP). Case Report A 69-year-old female with a past medical history of stage IIIB NSCLC (Status post chemoradiation followed by durvalumab therapy 3 months prior to admission), psoriatic arthritis (Discontinued infliximab 8 months ago and methotrexate 2 months prior to admission) and remote smoker but no underlying lung disease, presented to the emergency department with progressive dyspnea. She was initially hemodynamically stable but developed worsening hypoxemia, eventually requiring high-flow nasal cannula. Laboratory workup was significant for positive beta-d-glucan, but otherwise was unremarkable. Autoimmune testing revealed a positive P-ANCA but negative MPO and PR3 antibodies. Chest CT demonstrated diffuse bilateral perihilar ground-glass opacities notably in left upper lobe and known cavitation of left lower lobe mass, with imaging consistent with CIP. Bronchoscopy with bronchoalveolar lavage was notably positive for Pneumocystis jirovecii PCR, but negative for Direct Fluorescent Antibody (DFA), for which she was started on trimethoprim-sulfamethoxazole. Durvalumab was discontinued, and the patient required high-dose intravenous corticosteroids and three days of IVIG for her severe pneumonitis. Her oxygenation and symptoms slowly improved. She was discharged on a prolonged three-month prednisone taper and placed on trimethoprim-sulfamethoxazole prophylaxis during steroid therapy. Discussion This case highlights that P. jirovecii infection, whether active or colonizing, may serve as an immune trigger, amplifying pulmonary inflammation and precipitating or worsening durvalumab-associated pneumonitis. Linkage between P. jirovecii colonization and CIP development has not previously been explored. Our case suggests that PJP colonization or active infection may worsen the clinical course and outcomes of pneumonitis primarily driven by durvalumab and proposes that concomitant PJP infection be considered a novel risk factor for the severity of durvalumab-induced pneumonitis. This abstract is funded by: None
Winkelman et al. (Fri,) studied this question.