Letermovir for CMV Prevention After Lung Transplantation

Approximately 30 patients with IPF listed for lung transplantation will be enrolled and 15 are expected to undergo lung transplantation during the study period and receive the intervention. Patients who are CMV seropositive will receive letermovir for 6 months, patients who are CMV seronegative and receive lungs from a CMV seropositive donor (CMV D+/R-) will receive letermovir for 12 months. All patients will be followed for 12 weeks after completion of letermovir for the occurrence of CMV infection or disease after prophylaxis.

Historical controls will be LTRs for IPF from 2010-2019 who are CMV R+ or CMV D+/R- (donor positive/recipient negative). CMV prophylaxis in the historical controls was with valganciclovir for 6 months for CMV R+ and for 12 months for CMV D+/R-. Patients will be matched for CMV serostatus, induction immunosuppression, age, and telomere length.

Inclusion criteria

• Age ≥18 years on day of signing informed consent
• Listed for lung transplantation (single or double) due to a diagnosis of IPF or receipt of a lung transplant (single or double) for IPF in the 72 hours prior to enrollment
• Have a documented positive serostatus for CMV (CMV IgG seropositive, R+)
• Have a documented negative serostatus for CMV (CMV IgG seronegative, R-) and anticipate receiving or having received a lung allograft from a CMV IgG positive donor, D+). Only participants who are R+ or who are CMV D+/R- will receive intervention. Participants who are CMV D-/R- will be considered screen failures
• Able to travel to UPMC for routine post-transplant visits for a minimum of 15 months after transplantation
• Able to provide informed consent
• Be willing to use a contraceptive method while receiving LET and for at least 90 days following last dose of LET

Exclusion criteria

• Receipt of a previous solid organ transplant or hematopoietic stem cell transplant
• Multi-organ transplant recipient, i.e., heart-lung or lung-liver
• HIV seropositive
• HCV antibody or HCV RNA positive
• Donor HCV NAT positive
• Anticipated need for use of ganciclovir, valganciclovir, foscarnet, or cidofovir at the time of transplant
• Known or suspected hypersensitivity to LET or acyclovir
• CrCl < 10 ml/min or dialysis on day of transplant
• Child-Pugh Class C severe hepatic insufficiency
• Pregnancy or expected to conceive while on LET and through at least 90 days following cessation of LET