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.