IMPACT OF TRIKAFTA ON LUNG FUNCTION IN A CYSTIC FIBROSIS TRANSPLANT PATIENT

Abstract

SESSION TITLE: Fellows Transplantation Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Cystic fibrosis (CF) patients with at least one copy of F508del are eligible for Tezacaftor/Ivacaftor/Elexacaftor (Trikafta), a novel CFTR corrector/potentiator drug associated with increased lung function1 and likely improved sinus clearance. Trikata effects in lung transplant patients are unknown. We report a CF transplant patient, who developed reversible profound leukopenia, severely decreased lung function, and CT findings of peribronchial thickening and gas trapping after starting Trikafta for recurrent severe sinus disease. CASE PRESENTATION: A 30 year old CF female (homozygous F508del), underwent bilateral orthoptic lung transplant for end-stage lung disease and was treated with tacrolimus, azathioprine, prednisone valganciclovir, and sulfamethoxazole/trimethoprim for immunosuppression and infection prophylaxis. FEV1/FVC 3 months post-op were 3.36L/3.58L. Complaints of severe chronic sinusitis persisted and Trikafta was initiated with symptomatic benefit. 4 weeks later, she developed profound neutropenia, despite no antecedent changes in myelosuppressive drug therapy. Despite G-CSF, she was admitted with worsening respiratory symptoms and declining PFTs. She was afebrile with normal vital signs. Initial testing for bacterial and viral infections was negative. Azathioprine, Bactrim and Valcyte were held. Eravacycline was started empirically based on prior cultures. FEV1/ FVC declined to 2.62L/2.80L. Initial CT chest was essentially normal. Leucocyte counts slowly recovered with G-CSF. During this time, she began expectorating copious greenish ’sea-foam’ liquid. Repeat expiratory CT chest showed diffuse bronchial wall thickening and extensive air trapping. Bronchoscopy showed diffuse frothy secretions. Bronchoalveolar lavage had >80% return. Cell counts showed 100 nucleated cells/ml with benign differential. Following a negative cardiac and other etiologic workup, antibiotics were stopped and Trikata was discontinued as causation was suspected. Respiratory symptoms resolved and FEV1/FVC improved to supra-normal baseline over 2 weeks. DISCUSSION: Trikafta’s effect on transplanted lungs (where CFTR function is intrinsically normal) is unknown. Inflammatory cell-derived mediators are known to augment native CFTR function and increase airway epithelial cell fluid secretion in vitro2. We hypothesize that our patient’s symptoms and findings were due to exaggerated airway fluid secretion associated with repopulation of inflammatory cells. We propose that this led to airway edema, and bronchial wall thickening + gas trapping observed on imaging. Improvement in symptoms/PFTs after drug discontinuation support this. Etiology of profound leukopenia is less clear, though a previously undescribed direct drug-effect or altered GI absorption of other myelosuppressive medications are possible. CONCLUSIONS: Trikafta may have unexpected detrimental effects on a lung transplant physiology in CF patients Reference #1: Heijerman HGM, McKone EF, Downey DG, et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019. Reference #2: Abdullah LH, Coakley R, Webster MJ, et al. Mucin Production and Hydration Responses to Mucopurulent Materials in Normal versus Cystic Fibrosis Airway Epithelia. Am J Respir Crit Care Med. 2018; 197(4):481–491. doi:10.1164/rccm.201706-1139OC DISCLOSURES: No relevant relationships by Raymond Coakley, source=Admin input No relevant relationships by Christina Doligalski, source=Web Response No relevant relationships by Kunal Jakharia, source=Web Response No relevant relationships by leonard lobo, source=Web Response