Real world experience with conversion from valganciclovir to letermovir for cytomegalovirus prophylaxis: Letermovir reverses leukopenia and avoids mycophenolate dose reduction

Abstract

PurposeValganciclovir (VGC) is the gold‐standard for cytomegalovirus (CMV) prophylaxis (PPX) after solid organ transplant (SOT). Letermovir (LTV) was recently approved in high‐risk kidney transplant and has reduced myelosuppressive toxicity. Conversion from VGC to LTV may be pursued in the setting of leukopenia. It is unknown if this strategy is effective.MethodsAdult patients receiving abdominal SOT were included if converted from VGC to LTV between January 1, 2018 and January 31, 2023. Primary objective was to describe the impact of LTV conversion as measured by WBC recovery, mycophenolate modification, and use of GCSF, and prophylaxis efficacy assessed by course completion and breakthrough DNAemia. Secondary objective was to evaluate rates of post‐prophylaxis CMV.ResultsSeventy five SOT recipients met inclusion criteria. Mean change in WBC in response to LTV conversion by day 14 was +2.02 ± 2.52 k/uL. 75%(56/75) of the population did not require mycophenolate adjustment or had their dose increased after conversion. GCSF was required in 38.7%(29/75) prior to conversion; only 21.3%(16/75) of patients required GCSF after conversion. Early termination was uncommon, 14.7%(11/75) stopped due to lack of ongoing insurance approval, only one patient stopped due to adverse effects (1.3%). One patient had clinically significant breakthrough (1.3%) that was successfully managed with VGC. Incidence of post prophylaxis CMV was 40%.ConclusionWithholding of VGC with LTV conversion may improve leukopenia without need for additional supportive measures. Most importantly, this strategy avoided additional mycophenolate modifications. In our study, LTV was associated with low rates of breakthrough. Post‐prophylaxis CMV was similar to VGC prophylaxis.

Recent advances in cytomegalovirus infection management in solid organ transplant recipients

“…Letermovir is not recommended for treatment of CMV disease, due to low barrier for genotypic resistance [ 24 ]. Letermovir has been sporadically used as salvage therapy (before maribavir approval) for the treatment of refractory and resistant CMV with report of many clinical failures and on-treatment emergence of resistance, especially in the setting of CMV diseases with high viral loads [ 26 – 28 ]. Of note that use of letermovir as secondary prophylaxis has also been associated with high rates of failure [ 29 ].…”