The impact of progressive expansion of elexacaftor-tezacaftor-ivacaftor availability on lung transplant for cystic fibrosis in France.

BACKGROUND

Several countries reported a reduction in lung transplants for people with cystic fibrosis (pwCF) after elexacaftor-tezacaftor-ivacaftor (ETI) was introduced. We sought to evaluate how lung transplant indications evolved in relation to CFTR genotypes and the use of ETI.

METHODS

All lung transplants performed on pwCF in France between 2015 and 2024 were identified using data from the French Agence de la Biomédecine. Individual-level patient data, including CFTR genotypes and use of ETI at the time of transplant, were obtained from the French CF reference network centers.

RESULTS

Between 2015 and 2024, a total of 538 lung transplants were performed, including 461 first-time transplants and 77 re-transplants. The rate of first-time lung transplant was 13.4 per 1000 non-transplanted patients/year versus 1.8 per 1000 non-transplanted patients/year for 2015-2019 (prior to ETI availability) and 2020-2024 (following ETI availability), respectively (P < 0.0001); the rate of lung re-transplant was 10.2 per 1000 transplanted patients/year versus 7.7 per 1000 transplanted patients/year (P = 0.70). Treatment with ETI was prescribed prior to transplant in all F508del pwCF who received a first-time transplant since 2021 and in all those with non-F508del ETI-responsive variants since 2022. Eleven patients treated with ETI required lung transplant due to adverse effects leading to ETI discontinuation, concomitant severe liver disease or insufficient improvement of respiratory failure.

CONCLUSION

ETI has reduced, but not eliminated, the need for a first-time lung transplant in pwCF. Indications for a first-time lung transplant persist in a small subset of pwCF who respond to ETI and in those with nonresponsive CFTR genotypes. Re-transplant remains an option for selected transplant recipients with chronic lung allograft dysfunction.