ACUTE PULMONARY GRAFT VS HOST DISEASE RESPONDING TO IBRUTINIB THERAPY

Abstract

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Acute graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) usually involves the liver, skin and gut and lung involvement is rare. We report a case of acute GVHD with respiratory failure developing 18 months post allogeneic HSCT that was successfully treated with Ibrutinib. CASE PRESENTATION: A 58-year old male with relapsed small lymphocytic lymphoma (SLL) following matched, sibling-donor allogeneic HSCT complicated by chronic GVHD presented with acute onset shortness of breath following completion of slow corticosteroid taper. He presented 18 months post-transplant with a one-week history of progressive dyspnea, anorexia, weight loss, diarrhea, lower extremity edema, dizziness and lethargy. Dyspnea rapidly progressed to acute hypoxemic respiratory failure requiring high-flow oxygen therapy (HFOT). CT chest progressed from right middle and lower lobe ground glass opacities on admission to bilateral multi-lobar parenchymal opacities (Figure 1). Oxygen requirements progressed in spite of broad-spectrum antibacterial and antifungal therapy; he underwent bronchoscopy with transbronchial biopsy that showed chronic interstitial inflammatory infiltrate with scattered T cells, with no evidence of SLL/CLL (Figure 2). Microbiological testing, including bronchoalveolar lavage fluid cultures, was negative. The diagnosis of acute GVHD was made and the patient was started on high-dose IV methylprednisolone on hospital day (HD) 9. After 5 days, he remained on HFOT; he received tocilizumab and was started on ibrutinib on HD 14. By HD 18, his pulmonary status had significantly improved. By HD 22, he was off supplemental oxygen, and by HD 23, his chest CT demonstrated resolution of lung opacities. DISCUSSION: Non- infectious lung complications (NILC) is a nonspecific term that includes pulmonary edema, diffuse alveolar haemorrhage, idiopathic pneumonia syndrome, post-transplant lymphoproliferative disorder and many other pulmonary complications that can occur in patients post HSCT (1). Acute GVHD is one of the complications responsible for severe morbidity and often, mortality. As per the 2014 NIH consensus criteria, diagnosis of acute GVHD depends on clinical manifestations, not to the temporal relationship with transplantation (2). The clinical course of acute GVHD typically mimics steroid-responsive cryptogenic organizing pneumonia; however in certain cases, it may be refractory to even high doses of steroids. Our patient’s clinical improvement following initiation of immunomodulatory therapies including tocilizumab and ibrutinib, provides support for using these novel agents. CONCLUSIONS: Ibrutinib is a tyrosine kinase inhibitor that has been shown to benefit patients with chronic GVHD (3). Our case highlights its use with a positive outcome in acute GVHD refractory to steroids. Reference #1: Pena E, Souza CA, Escuissato DL, Gomes MM, Allan D, Tay J, et al. Noninfectious pulmonary complications after hematopoietic stem cell transplantation: practical approach to imaging diagnosis. Radiographics. 2014;34(3):663-83. Reference #2: Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389-401.e1. Reference #3: Miklos D, Cutler CS, Arora M, Waller EK, Jagasia M, Pusic I, et al. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 2017;130(21):2243-50. DISCLOSURES: No relevant relationships by Divyansh Bajaj, source=Web Response No relevant relationships by Nancy Hardy, source=Web Response No relevant relationships by Van Holden, source=Web Response No relevant relationships by Shreya Kanth, source=Web Response No relevant relationships by Akshay Kohli, source=Web Response No relevant relationships by Laura Malone, source=Web Response Consultant relationship with Medtronic Please note: $1001 - $5000 Added 03/17/2019 by Edward Pickering, source=Web Response, value=Consulting fee Consultant relationship with Medtronic Please note: $1001 - $5000 Added 03/13/2019 by Ashutosh Sachdeva, source=Web Response, value=Consulting fee Unrestricted education grant relationship with Olympus Please note: $1001 - $5000 Added 03/13/2019 by Ashutosh Sachdeva, source=Web Response, value=Grant/Research Support