SEVERE NONINFECTIOUS PNEUMONITIS ASSOCIATED WITH IBRUTINIB FOR DIFFUSE LARGE-B-CELL LYMPHOMA

Abstract

TOPIC: Diffuse Lung Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Ibrutinib is an oral Bruton's tyrosine kinase inhibitor that is indicated in treatment of certain lymphomas and is now being investigated for primary CNS diffuse large B-cell lymphoma (DLBCL). We present a case of severe non-infectious pneumonitis in a patient receiving ibrutinib for recurrent primary CNS DLBCL CASE PRESENTATION: A 51-year-old male with primary CNS DLBCL was treated with ibrutinib in a clinical trial after failure of first line and salvage therapies. Seven weeks after initiation of the drug, patient presented with dyspnea, tachypnea, tachycardia, and encephalopathy to the hospital. Shortly after admission, patient developed worsening hypoxia and encephalopathy requiring intubation and mechanical ventilation. Labs demonstrated mild anemia and elevated LDH without leukocytosis or thrombocytopenia. Blood cultures and nasopharyngeal PCR for SARS-CoV-2 were negative. CT chest showed non-specific upper lung predominant extensive bilateral ground glass opacities with patchy consolidation. Differential diagnosis included infectious and inflammatory etiologies. Bronchoalveolar lavage was negative for viral, mycobacterial, fungal or bacterial pathogens. Ibrutinib was discontinued and patient was treated with 60 mg intravenous methylprednisolone daily. Patient's was successfully extubated with resolving hypoxia. DISCUSSION: Common adverse effects from treatment with ibrutinib include diarrhea, hypertension, fatigue, infections, and atrial fibrillation. Although infectious pneumonias have been documented, only a few accounts of non-infectious pneumonitis have been reported in the extant medical literature. Both non-specific interstitial pneumonia and organizing pneumonia cases have been reported. Early recognition in appropriate clinical context, discontinuation of offending drug, and treatment with steroids is warranted. CONCLUSIONS: Patients on targeted therapy with Ibrutinib are at risk of developing severe hypoxic respiratory failure from non-infectious pneumonitis. Timely consideration, treatment with steroids and ventilatory support can help with recovery. REFERENCE #1: 1. Mato AR, Islam P, Daniel C, Strelec L, Kaye AH, Brooks S, et al. Ibrutinib-induced pneumonitis in patients with chronic lymphocytic leukemia. Blood. 2016;127(8):1064-7. REFERENCE #2: 2. Murthy V, Suh J, Bradshaw A-d, Sloance M. Ibrutinib-Induced Rapidly Progressive Inflammatory Pneumonitis. C51 TOXIC INGESTIONS AND EXPOSURES. p. A4584-A. REFERENCE #3: 3. Blackwell L, Cai D, Srinivas S, Lovoulos C, Kim J. Ibrutinib-Induced Organizing Pneumonia. CHEST. 2016;150(4):782A. DISCLOSURES: No relevant relationships by zainub ajmal, source=Web Response No relevant relationships by Gowthami Kobbari, source=Web Response No relevant relationships by Fatima Tuz Zahra, source=Web Response No relevant relationships by Gregory Wu, source=Web Response