IBRUTINIB-INDUCED INTERSTITIAL LUNG DISEASE IN A PATIENT WITH CHRONIC LYMPHOCYTIC LEUKEMIA

Abstract

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Chronic Lymphocytic Leukemia (CLL) is a neoplasm of dysfunctional lymphocytes. Ibrutinib, a Bruton’s tyrosine kinase inhibitor, has been a favored treatment for CLL because of its great efficacy in inducing a rapid decrease in lymph node size with a relatively minimal side effect profile, which includes fatigue, diarrhea, and thrombocytopenia. In this case, we present a patient found to have acute respiratory failure secondary to interstitial lung disease (ILD) shortly after initiating therapy with Ibrutinib. CASE PRESENTATION: A 93-year-old female with CLL who presented to the emergency department with a 3-day history of progressively worsening dyspnea and productive cough with green sputum appreciated 1-week after starting Ibrutinib. She was in acute hypoxemic respiratory failure, saturating at 81% on ambient air. A Computed Tomography Angiography (CTA) of the chest was performed. It revealed diffuse bilateral ILD with honeycombing in the right upper lung and a large left sided pleural effusion. These findings were new compared to a CT of the lung done four months prior. Analysis of the effusion fluid revealed a malignant etiology. A chest tube was placed. She was treated with steroids as well as empiric antibiotics for pneumonia. She had subsequent improvement of her respiratory failure and was ultimately discharged in stable condition. Ibrutinib was not restarted due to patient’s frailty. A follow up CT done four months after discharge showed resolution of ILD. DISCUSSION: Pulmonary complications of Ibrutinib, while rare, have been previously reported. Most of these complications have been limited to pneumonia and pulmonary infiltrates, seen in 2% of patients in one study [1], and dyspnea seen in patients with pre-existing chronic obstructive pulmonary disease, pulmonary fibrosis, and malignant pleural effusions [2]. To the best of our knowledge, there has only been one reported case [3] of a patient with healthy lungs who experienced acute respiratory failure secondary to ILD that occurred one week after the initiation of Ibrutinib for mantle cell lymphoma. While acknowledging the limitation of evidence provided by two case reports, ILD is a consideration in patients receiving Ibrutinib who present with respiratory complaints. CONCLUSIONS: We present a 93-year-old patient who, after recently starting Ibrutinib for CLL, experienced acute hypoxemic respiratory failure with radiographic findings consistent with ILD. Ibrutinib was discontinued and the patient made a successful recovery after being treated with steroids, antibiotics, and chest tube placement. Based on this case and another one that reports similar findings, we recommend monitoring patients receiving Ibrutinib for respiratory adverse events. Reference #1: Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial. Farooqui MZ, Valdez J, Martyr S, Aue G, Saba N, Niemann CU, Herman SE, Tian X, Marti G, Soto S, Hughes TE, Jones J, Lipsky A, Pittaluga S, Stetler-Stevenson M, Yuan C, Lee YS, Pedersen LB, Geisler CH, Calvo KR, Arthur DC, Maric I, Childs R, Young NS, Wiestner A Lancet Oncol. 2015 Feb; 16(2):169-76. Reference #2: Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results. Wang ML, Blum KA, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Zhang L, Baher L, Cheng M, Lee D, Beaupre DM, Rule S. Blood. 2015 Aug 6; 126(6):739-45. Reference #3: Jungmann S, Ludwig WD, Schönfeld N, et al. A Patient with Non-Hodgkin Lymphoma and Nonspecific Interstitial Pneumonia during Ibrutinib Therapy. Case Rep Oncol Med. 2017;2017:5640186. DISCLOSURES: No relevant relationships by Phillip Berges, source=Web Response No relevant relationships by Najia Hussain, source=Web Response No relevant relationships by Kashif Hussain, source=Web Response No relevant relationships by Samer Ibrahim, source=Web Response No relevant relationships by Nandini Seshan, source=Web Response No relevant relationships by Deepali Sharma, source=Admin input