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Observational Study
. 2023 Mar;25(2):225-232.
doi: 10.1007/s40272-022-00547-6. Epub 2022 Dec 27.

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

Katharina F Körholz #  1 , Miriam A Füller #  1 , Marc Hennies  2 , Malcolm Holterhus  1 , Susanne Hagedorn  1 , Martina Ahlmann  1 , Heike Thorer  1 , Birgit Burkhardt  1 , Andreas H Groll  3
Affiliations
Observational Study

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

Katharina F Körholz et al. Paediatr Drugs. 2023 Mar.

Abstract

Background: Cytomegalovirus (CMV) infection is a frequent event in patients undergoing allogeneic haematopoietic cell transplantation (HCT) and is associated with increased morbidity and mortality due to eventual progress to end-organ disease. Letermovir prophylaxis for CMV infections has become a standard of care in adult HCT recipients due to its efficacy and high tolerability. However, it is not yet approved for paediatric patients.

Objective: In a retrospective single-centre observational study we evaluated the use of letermovir for prophylaxis or pre-emptive treatment of cytomegalovirus (CMV) infection in seropositive paediatric HCT recipients receiving the compound outside of clinical trials. The primary endpoint was CMV reactivation requiring a change of medication.

Methods: A total of 17 patients (seven female/ten male; median age 12.2 [range 3.5-19] years, median body weight 39.5 [range 15-63] kg; median follow-up time 463.7 [range 41-1022] days) were identified who were started on oral (14) or intravenous (3) followed by oral (2) letermovir shortly after neutrophil engraftment at doses determined on the basis of age, weight, and concomitant cyclosporine use.

Results: Five patients had no evidence of viral replication (prophylactic use), while 12 patients had varying extents of viral replication (pre-emptive therapy). A change of therapy was required in one patient due to a sustained increase in CMV viral load, and in two patients, letermovir was stopped without later reactivation after initiation of palliative care for recurrent leukaemia. Of the 14 patients who completed treatment, 3 had evidence of transient viral replication after end of treatment that required no further antiviral treatment. No patients (of 17) discontinued letermovir due to an adverse event.

Conclusion: Letermovir was effective in controlling CMV infection in seropositive paediatric allogeneic HCT recipients and was overall well tolerated. Pending completion of the still ongoing paediatric investigation plans, letermovir will be an important adjunct to our options for control of infectious complications in this special population.

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Conflict of interest statement

AHG has received grants from Gilead, Merck, Sharp & Dohme and Pfizer and has served as consultant to Amplyx, Astellas, Basilea, F2G, Gilead. Merck, Sharp & Dohme, Pfizer, Scynexis, and Mundipharma. KFK, MAF, MTH, MH, SAH, MA, HT and BB have no conflicts to declare.

Figures

Fig. 1
Fig. 1
Course of CMV viral load in plasma over time in 17 patients receiving letermovir between July 2019 and March 2022 off-label for prophylaxis or pre-emptive treatment. In each plot, CMV viral replication at transplant day ± 5 days, at the start of letermovir treatment, at the end of letermovir treatment and in between, the maximum observed value while on letermovir therapy with letermovir is depicted. Each line represents one individual patient. (a) CMV viral load in plasma in IU/mL over time in five patients with no evidence of viral replication at the time of start of treatment. * Patient (5) died before end of treatment. (b) CMV viral load in plasma in IU/mL over time in 12 patients with evidence of viral replication at the time of start of treatment. * Patient (14) died before end of treatment. ∆ Patient (13) was changed to ganciclovir treatment. CMV cytomegalovirus, LTV letermovir
Fig. 2
Fig. 2
Diagram depicting the descriptive results concerning viral replication status and LTV treatment status. CMV cytomegalovirus, LTV letermovir
See this image and copyright information in PMC

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