(1235) An Emerging Culprit of Diffuse Alveolar Hemorrhage: Irinotecan Therapy

Introduction: Irinotecan is a topoisomerase I inhibitor used in the treatment of various solid cancers. It can cause pneumonitis, either alone or in combination with other drugs or radiotherapy. Pulmonary toxicity was reported in >20% of patients when irinotecan was used in combination with 5-fluorouracil (5-FU). We describe a rare case of diffuse alveolar hemorrhage (DAH) likely caused by irinotecan in a patient with pancreatic cancer which resolved with pulse dose steroids.

Description: A 75-year-old male with advanced pancreatic adenocarcinoma presented with worsening dyspnea 6 days after his last chemotherapy with irinotecan and 5-FU. He was afebrile and hemodynamically stable. He was hypoxemic with oxygen saturation of 70% on room air. Chest radiograph showed bilateral patchy opacities with vascular congestion. Chest computed tomography(CT) revealed new diffuse bilateral ground glass opacities with no evidence of pulmonary embolism. Respiratory viral panel and COVID-19 PCR were negative. His hypoxic respiratory failure was attributed to likely pneumonia and fluid overload. Initial treatment with antibiotics, furosemide, bronchodilators, and methylprednisolone was ineffective. He required intubation for worsening hypoxemia and increased work of breathing. Bronchoscopy with bronchoalveolar lavage (BAL) was performed and noted clear airways with DAH. The patient was initiated on high-dose methylprednisolone 1 gram IV daily for 3 days. Connective tissue disease and BAL infectious workup were negative. BAL cytology noted reactive epithelial cells with 70% neutrophils. He improved and was extubated 4 days later, and steroids gradually tapered. Follow-up CT on Day 12 showed marked resolution of the ground glass opacities. The patient was discharged home on room air to complete the steroid taper and follow-up in pulmonary clinic. Irinotecan was discontinued from his treatment regimen.

Discussion: Irinotecan-induced DAH is a rare pulmonary toxicity with only two previous cases reported. The pathogenesis remains unclear but thought to involve either direct drug injury to alveolar micro-capillaries, indirect inflammatory effects, or an immunological mechanism. Rapid diagnosis of exclusion, discontinuation of irinotecan, and treatment with high-dose steroids is key to optimizing patient outcomes.