Use of Letermovir as Salvage Therapy for Drug-Resistant Cytomegalovirus Retinitis

Abstract

Treatment options for drug-resistant cytomegalovirus (CMV) are limited. Letermovir is a novel antiviral recently approved for CMV prophylaxis following hematopoietic cell transplantation, but its efficacy in other settings is unknown. We recently used letermovir for salvage treatment in four solid organ transplant recipients with ganciclovir-resistant CMV retinitis. All patients improved clinically without known adverse drug events. However, three patients failed to maintain virologic suppression, including two patients who developed genotypically confirmed resistance to letermovir while on therapy.

Letermovir and its role in the prevention of cytomegalovirus infection in seropositive patients receiving an allogeneic hematopoietic cell transplant

“…47 Lastly, Turner et al described the use of high dose letermovir (720-960 mg) as salvage therapy for ganciclovir-resistant CMV retinitis in four solid organ transplant recipients. 48 Whereas all patients experienced clinical improvement, with resolution of retinitis, three had recurrence of CMV DNAemia and two developed resistance to letermovir (UL56). 48 These overall mixed results highlight the need for careful consideration when using letermovir off label, especially in the setting of treatment, given concerns about the development of resistance.…”

“…48 Whereas all patients experienced clinical improvement, with resolution of retinitis, three had recurrence of CMV DNAemia and two developed resistance to letermovir (UL56). 48 These overall mixed results highlight the need for careful consideration when using letermovir off label, especially in the setting of treatment, given concerns about the development of resistance. More clinical studies are needed to further elucidate the role of letermovir in both HCT and solid organ transplant recipients for the treatment of CMV DNAemia or CMV end-organ disease.…”

Reply to Frange and Leruez-Ville, “Caution Is Required before Recommending Wide Use of Letermovir as Salvage Therapy for Cytomegalovirus Diseases”

“…W e thank Dr. Frange and Dr. Leruez-Ville for their comments regarding our recent article (1). First, due to the inherent limitations of a case series, we agree that it is impossible to rule out potential confounding benefits from concurrent intravitreal treatments.…”

Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy

“…Notably, in the phase 3 prophylaxis study, 48 patients with detectable CMV viremia (viral load in all cases < 1000 copies/mL) prior to randomization received letermovir, thereby essentially receiving letermovir as preemptive therapy; of those, approximately 33% had clinically significant CMV infection by week 14 [22••, 39]. Additionally, concerns exist about the relatively low barrier to resistance in vitro, and emerging reports describe the development of resistance when used in the setting of active infection [40][41][42][43]. An ongoing clinical trial (NCT03728426) will evaluate the safety and efficacy of letermovir as salvage treatment of CMV infection or disease.…”