As Lung Transplants Decline, Nonwhite Patients Still in Need
Availability of CFTR modulator therapies likely a factor, researchers say
A recent overall decline in lung transplant rates for adults and children with cystic fibrosis (CF) in the U.S. has had less impact on nonwhite patients, according to a recent analysis.
While transplant rates have decreased in the past couple years for all people with CF, the declines were steeper among white patients than nonwhite patients, data show.
These findings may be related to the recent emergence of the highly effective CFTR modulator therapy Trikafta (elexacaftor/tezacaftor/ivacaftor), for which white patients are more likely to be eligible due to their underlying genetic cause of disease, researchers noted.
The study, “Changing racial and ethnic differences for lung transplantation in cystic fibrosis,” was published as a brief communication in the journal Pediatric Transplantation.
As new CFTR modulators have emerged for treating CF, a large proportion of patients have access to highly effective therapies.
In particular, Vertex Pharmaceuticals’ triple combo therapy, Trikafta, offers a treatment option for patients who have at least one copy of the F508del mutation in the CFTR gene — the most common CF-causing mutation affecting about 90% of all patients. In the U.S., it also is approved for certain other mutations that have been shown to be responsive to the medication in laboratory studies.
With the preservation of lung function that results from using Trikafta and other CFTR modulators, patients now may be at a lower mortality risk and need fewer lung transplants than in years before these treatments were available.
To that end, a number of studies have shown that the number of lung transplants in CF patients has decreased notably in recent years. But none of these studies addressed whether there are racial or ethnic disparities in these transplant rates.
To address this, researchers in Cincinnati examined transplant trends among CF patients in the U.S. using data from the United Network for Organ Sharing (UNOS) registry.
The team extracted data from children and adults with CF who underwent a lung transplant in the U.S. from October 1987 to December 2021, and compared the transplant rates of white patients to those of nonwhite patients, including Black, Hispanic-Latino, Asian, American Indian, Native, and Pacific-Islander populations.
Overall, a significant reduction in annual lung transplants was observed for both children and adults in 2020 and 2021, the first years after Trikafta’s 2019 U.S. approval.
The annual mean number of transplants was 23.2 for CF children from 1990–2019, compared with five in 2020 and four in 2021. Similarly to children, transplant rates decreased over time in CF adults. Specifically, the mean annual number of transplants was 144.9 from 1990–2019, compared with 73 in 2020 and 45 in 2021.
From 1990 to 2019, 696 CF children underwent lung transplants, which made up 50.5% of the pediatric population undergoing such procedure. After 2019, CF children made up 16.4% of transplants (nine of 55 children).
Of 39,542 transplants occurring in adults from 1990 to 2019, 4,773 involved CF patients (12.1%). After 2019, 118 of 5,004 transplants occurred in CF patients, amounting to 2.4%.
The Trikafta connection
“Although CFTR modulator treatment is not collected by the UNOS Registry, the timing of this change in the number of [lung transplants] in CF suggests that [Trikafta] is a major contributing factor,” the researchers wrote.
Still, racial and ethnic differences in transplant rates were observed. Transplant rates in white children decreased from 49.5% of all pediatric transplants from 1990 to 2019, to 8.3% after 2019, a difference of 41.2%. In nonwhite children, rates have gone from 33.5% to 22.5%, or a difference of 11%.
Similarly, rates decreased from 13% to 2.6% in white CF adults, compared with 3.9% to 1.5% in non-white patients, amounting to a 10.4% difference for white patients and a 2.4% difference for non-whites.
These greater declines among white patients could be explained by eligibility for Trikafta or other CFTR modulators, the researchers noted, with nonwhite patients less likely to have eligible mutations, particularly F508del.
“[Trikafta] therapy will be less impactful for this patient population,” the researchers wrote.
“Due to minorities representing a proportion of the CF population having a worse disease burden and increased mortality, the need to optimize referral and listing practices for [lung transplant] remain for this patient population until there are alternative therapies for the treatment of their chronic lung disease,” they added.