Off-Label Use of Letermovir as Preemptive Anti-Cytomegalovirus Therapy in a Pediatric Allogeneic Peripheral Blood Stem Cell Transplant

Abstract

Despite the effectiveness of the currently available antiviral drugs in treating cytomegalovirus (CMV) infection, high rates of adverse effects are associated with their use. Moreover, a problem of increasing importance is the emergence of drug-resistant CMV infection. Here, we describe the first case of off-label use of letermovir (LMV) as preemptive antiviral therapy, in a pediatric allogeneic peripheral blood stem cell transplant recipient with ganciclovir-resistant CMV infection who was intolerant to foscarnet and unable to achieve viral clearance after seven doses of cidofovir. After the administration of LMV, a gradual reduction in viral load was observed and within 6 weeks of LMV treatment, after more than 6 months of positive CMV-DNAemia, the patient cleared the infection. No adverse effects associated with LMV were observed during treatment. In this pediatric study case, the offlabel use of LMV for the treatment of CMV infection has been well tolerated and proved to be effective in leading to the suppression of viral replication.

Letermovir use in children after hematopoietic cell transplantation: summary of reported data

“…We found nine reports that fulfilled the search criteria, published between 2019 and 2022 (Table I) [1,[4][5][6][7][8][10][11][12]. The total number of cases involved in research was 46, with the patients' ages ranging from 2 to 19 years.…”

“…CMV infection is associated with higher non-relapse mortality (NRM) and all-cause mortality [3]. CMV reactivation happens in up to 70% of CMV-seropositive recipients (R+) [4,5]. The most common clinical manifestations of CMVi in HSCT patients include pneumonia, hepatitis, enteritis, retinitis and bone marrow suppression.…”

“…Studies on LMV used as primary prophylaxis proved its high efficacy at reducing the incidence of CMV disease and the number of deaths caused by CMVi [2][3][4][5][6][7]11]. In 2017, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved LMV for primary prophylaxis in CMV-seropositive adult patients undergoing allogeneic HSCT (allo-HSCT) [2-8, 10, 11].…”

“…However, it was not registered for CMVi preemptive treatment, CMVi secondary prophylaxis, or the treatment of CMV disease [2,3,7]. There is very limited data regarding LMV's use in pediatric patients as it has not been approved so far as any kind of treatment in children, with its use remaining off label [1][2][3][4][5][6][7][8][10][11][12]. The aim of this study was to summarize reported data on the efficacy and safety of LMV in pediatric patients.…”

Letermovir for Prophylaxis and Pre-emptive Therapy of Cytomegalovirus Infection in Paediatric Allogeneic Haematopoietic Cell Transplant Patients

“…Most patients included in this study (70%) received letermovir per definition as pre-emptive treatment following documented CMV reactivation, and most responded very well to letermovir treatment. There are only few reports for letermovir pre-emptive therapy or secondary prophylaxis in children, which show, however, overall high viral clearance rates [ 16 , 28 , 29 ]. In adult patients, a Phase 2a study was conducted for pre-emptive letermovir treatment in kidney transplant recipients [ 30 ] and experiences with letermovir secondary prophylaxis in HSCT recipients have been previously published [ 16 , 31 ].…”