A CASE REPORT OF IBRUTINIB-INDUCED PNEUMONITIS

Abstract

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Ibrutinib irreversibly inhibits Bruton's tyrosine kinase, an essential component of B-cell receptor signaling, leading to diminished proliferation and survival of malignant B-cells. Ibrutinib is used to treat leukemias and lymphomas, including chronic lymphocytic leukemia (CLL). Several complications are associated with ibrutinib, below describes a case of ibrutinib induced pneumonitis. CASE PRESENTATION: 64-year-old female recently diagnosed with CLL and started on ibrutinib therapy. Two months later, patient was admitted for progressive dyspnea and nonproductive cough. Initial work-up showed hypoxia, lymphocytic leukocytosis, negative COVID and respiratory viral pathogen panel (RVP). Computed tomography (CT) of chest showed new bilateral ground-glass opacities compared to CT scan three months earlier. She was initially treated with ceftriaxone and azithromycin. Patient had worsening respiratory status and required intubation on day four. Patient did not improve with several antibiotics and antifungals. But given history and borderline elevated beta-D-glucan, she underwent bronchoscopy due to concern for fungal infection. All studies including tuberculosis, histoplasma, aspergillus, coccidioides, blastomyces, pneumocystis jiroveci, fungal and bacterial cultures were negative. All antimicrobials were stopped. Patient had spontaneous pneumothoraxes on hospital day 13 and 15 requiring left needle decompression and bilateral chest tube placement. A sputum culture was repeated which grew few multi-drug resistant pseudomonas. She was treated with 7-day course of meropenem without improvement. Repeat workup showed bilateral ground-glass opacities, negative COVID, RVP, and bronchoscopy with negative fungal antigens, bacterial and fungal cultures. Given concern for ibrutinib induced pneumonitis, steroids were started with subsequent weaning from ventilator support to room air. DISCUSSION: Pneumonitis and pneumothorax are rare complications of ibrutinib therapy. The new ground-glass opacities, not present on imaging prior to starting ibrutinib, dyspnea and hypoxia, no prior lung disease, and no other new medications, is concerning for ibrutinib associated pneumonitis. Infection did not cause the opacities, both extensive infectious workups were unremarkable. The pseudomonas sputum culture was likely colonization from prolonged intubation, as she was afebrile, had stable leukocytosis, and treatment did not change respiratory status. Patient also had spontaneous pneumothoraces on lung protective ventilation. She has no history of pneumothorax, nor underlying condition that would lead to pneumothorax. In addition, oxygenation improved after starting steroids. She was weaned from ventilator support to room air, further supporting ibrutinib associated pneumonitis. CONCLUSIONS: Pneumonitis is a rare, notable complication of ibrutinib therapy. REFERENCE #1: Rai, K. R., MD, & Stilgenbauer, S., MD. (2021, January 07). Selection of Initial Therapy For Symptomatic or Advanced Chronic Lymphocytic Leukemia. Retrieved from https://www.uptodate.com/contents/selection-of-initial-therapy-for-symptomatic-or-advanced-chronic-lymphocytic-leukemia?search=ibrutinib pneumonitissIbrutinib-induced pneumonitis in patients with chronic lymphocytic leukemia. Blood 2016;127 (8): 1064–1067. doi: https://doi.org/10.1182/blood-2015-12-686873 DISCLOSURES: No relevant relationships by Tyler Cooper, source=Web Response No relevant relationships by Lauren Sesemann, source=Web Response