Letermovir should be first-line cytomegalovirus prophylaxis in lung transplant recipients

Universal cytomegalovirus (CMV) prophylaxis is recommended for at-risk lung transplant recipients. Valganciclovir (VGCV) is currently the preferred first-line agent. VGCV-related myelosuppression, however, can lead to drug discontinuation or reduction in antimetabolite immunosuppression. Variable VGCV pharmacokinetics in the setting of renal injury are also associated with development of resistant CMV. Letermovir, a newer anti-CMV agent, is an attractive alternative for first-line prophylaxis in many lung transplant recipients. Initially investigated in bone marrow transplant, there are now multiple retrospective studies of lung transplant recipients who were switched from VGCV to letermovir because of tolerability, dosing, or resistance. These studies have reaffirmed the safety and efficacy of letermovir in the lung transplant population. Despite this, letermovir continues to be recommended as second-line prophylaxis with use limited to those who fail VGCV. We argue that there are now sufficient data to support letermovir use in lung transplant recipients at high risk of VGCV toxicity. This includes patients with renal insufficiency, of advanced age, and with cytolytic immunosuppression, high risk of rejection, and telomere biology disorders, among other conditions. First-line letermovir would reduce the risk of VGCV-related myelosuppression and attendant reduction in immunosuppression, as well as development of CMV resistance due to variable renal function and VGCV pharmacokinetics.