Elexacaftor/Ivacaftor/Tezacaftor in Lung Transplant Recipients: A Case Series

Purpose Little data is published describing the safety or efficacy of elexacaftor/ivacaftor/tezacaftor in lung transplant recipients. Even though it is not expected to offer pulmonary benefits in lung transplant recipients with cystic fibrosis (CF), it may improve extrapulmonary manifestations. Methods This retrospective case series summarizes the clinical experience of 7 lung transplant recipients on elexacaftor/ivacaftor/tezacaftor therapy. Results Patients were 39 +/- 11 years old, 71% male, and 7.6 +/- 7 years post transplant when starting elexacaftor/ivacaftor/tezacaftor. After 211 +/- 89 days on therapy, 4 (57%) note improvement in at least one domain: 4 (47%) report improved GI symptoms, 2 (29%) report improvement in sinus symptoms, 2 (29%) had pancreatic enzyme dose reductions. Of the 5 patients with CF-related diabetes, 3 (40%) report improvement in diabetes control. Most patients required a tacrolimus dose reduction after starting elexacaftor/ivacaftor/tezacaftor. In order to maintain the same tacrolimus trough goal, doses were adjusted from 9.3 +/- 5.9 mg/day at baseline to 7.4 +/- 5.3 mg/day after dose titration was complete; this was an average 20% dose reduction. There were no cases of allograft rejection. With regard to drug-related side effects severe enough to warrant intervention, 2 (29%) experienced leukopenia and 1 (14%) experienced transaminitis. Of the two with leukopenia, one improved with dose adjustment to other medications whereas one required elexacaftor/ivacaftor/tezacaftor discontinuation. The discontinuation rate for any cause was 1 patient (14%). Conclusion In sum, elexacaftor/ivacaftor/tezacaftor may offer a benefit for management of the extrapulomonary manifestations of cystic fibrosis after lung transplantation. Enhanced monitoring for tacrolimus dose adjustments and drug-related side effects is warranted.