The Changing Face of Lung Transplant Waiting Lists in the Era of CFTR Modulators

Purpose Cystic fibrosis (CF) is a life-limiting genetic condition with which often leads to life-threatening respiratory failure requiring lung transplantation. People with CF (PwCF) account for 16% of adult bilateral lung transplants internationally according to a 2016 report of the ISHLT Registry by Yusen et al. With the advent of effective CFTR (cystic fibrosis transmembrane conductance regulator) modulators becoming widely available in recent years, for many PwCF the clinical response has been transformative, and a significant proportion no longer meet criteria for lung transplantation referral and listing. Methods A retrospective analysis was undertaken of the number of PwCF referred in the last 12 months (i.e. since the CFTR modulators tezacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor became widely available in the UK) compared to the previous 3 years, for lung transplantation at Harefield Hospital. The impact of CFTR modulators on the Lung Transplant Waiting List at Harefield Hospital was also assessed. Results As of October 2020, of the 25 PwCF who were assessed for lung transplantation and met criteria for listing at time of assessment, only 7 (28%) remain actively listed. All of the others (n=18; 72%) were suspended after starting a CFTR modulator (of which 12 were suspended in the last 12 months). Median improvement in FEV1(%) after starting a modulator in those who subsequently suspended was 10% (range 0-24%). Referrals of PwCF in the last 12 months was 22 compared with an average of 37 referrals per year over the preceding 3 years. Only 14% (7/49) of the current active waiting list for double lung transplantation are PwCF compared with 26% (19/73) a year ago. Conclusion The improvement in quality of life and lung function in PwCF eligible for CFTR modulators can be transformative. However, those who continue to decline despite this treatment, are likely to be older, have multiple CF-related comorbidities, and may be more complex surgical candidates. Transplant centres face a changing landscape as transplant lists become increasingly populated with other patient groups. Those continuing to transplant PwCF need to become experienced at managing complex CF comorbidities.