Case 8
A 21-year-old male with CF (F508del/F508del) status post liver
transplant in 2012 for CFLD, complicated by post-transplant
lymphoproliferative disorder (PTLD) diagnosed one-year post-transplant,
which was successfully treated with rituximab. He has not had any issues
with rejection since this time. His immunosuppression regimen includes
sirolimus and prednisone. The patient was previously treated with
lumacaftor/ivacaftor (lum/iva) and was transitioned to elx/tez/iva at
the end of November 2019. Due to a stable hepatic panel on standard
dosing of lum/iva, he was initiated on full-dose of elx/tez/iva. LFTs,
bilirubin and sirolimus concentrations were scheduled for weekly
monitoring after initiation of elx/tez/iva, however the patient was
noncompliant with ordered frequency of blood draws, and initially,
communication regarding aberrant labs was not successfully relayed
between the liver transplant and CF providers. Therefore, due to
unfamiliarity with this new CFTR modulator, when the patient’s liver
enzymes began to rise, the liver transplant team grew concerned for
rejection. The patient was sent for liver biopsy on December 2019,
which came back normal. A month later, the CF team was notified of
significant elevations of up above 5 times the ULN in AST and ALT. Based
on these elevations and concern for drug-induced hepatic impairment,
elx/tez/iva dose was reduced to 2 tablets daily. After dose reduction,
LFTs significantly improved. The patient’s sirolimus concentration also
increased significantly after the switch from lum/iva to elx/tez/iva,
from 12.0 ng/mL (goal: 3-20 ng/mL) to 24.1 ng/mL about 2 weeks
later. Initially no change was made to sirolimus dose, despite
discontinuation of the inducer lum/iva, which is likely what caused this
jump in sirolimus concentration. The patient’s sirolimus dose was
incrementally reduced and returning to his dosing before lum/iva
initiation, with sirolimus concentration returning to normal range. The
patient’s baseline ppFEV1 was 63%, and after 3 months
of therapy with elx/tez/iva, increased to 71%, with corresponding
improvement in symptoms and quality of life.