Letermovir conversion after valganciclovir treatment in cytomegalovirus high‐risk abdominal solid organ transplant recipients may promote development of cytomegalovirus‐specific cell mediated immunity

Abstract

Purpose: To evaluate the association of conversion from valganciclovir to letermovir on cytomegalovirus-specific cellular immunity.Methods: Adult patients were included if they received a kidney or liver transplant between 8/1/2018-12/31/20, developed symptomatic, high-level CMV viremia and were converted to letermovir 480 mg daily as monotherapy after treatment with ganciclovir-derivatives for a minimum of 4 weeks and had subsequent CMV cellmediated immunity (CMI) testing via ICS assay by flow cytometry (Viracor Eurofins T Cell Immunity Panel).Results: Seven patients met inclusion criteria; 87.5% were male and recipients of a kidney transplant. All patients were CMV high risk (D+/R-). Mean time from transplant to CMV disease was 200 ± 91 days. Peak viral load (VL) during CMV treatment was 540,341 ± 391,211 IU/mL. Patients received a mean of 30 ± 24 weeks (range: 4-78 weeks) of therapy with ganciclovir-derivatives at induction doses prior to letermovir introduction. The median absolute lymphocyte count (ALC) at letermovir initiation was 400/μL (IQR 575) and the median VL was 51.6 (range: ND-490) IU/mL. Most patients (n = 5/7, 71.4%) experienced an increase in VL 1 and/or 2 weeks after conversion to letermovir. All patients had positive CMI per ICS assay after conversion.Patients received a mean of 10.3 ± 6.9 weeks of letermovir prior to having a positive result. Median ALC at positivity was 900/μL. Immunosuppression was not further reduced from initiation of letermovir to demonstration of CMV CMI. No patient had progressive replication or breakthrough disease while maintained on letermovir and three patients (42.9%) underwent antiviral withdrawal without recurrence at the last follow-up. Conclusion:In this case series of abdominal transplant recipients with severe or persistent CMV infection, patients developed CMV-specific CMI after conversion to letermovir monotherapy. These data suggest that using letermovir in place of valganciclovir for secondary prophylaxis may address the lack of efficacy previously seen with this

Cytomegalovirus Management in Solid Organ Transplant Recipients: A Pre-COVID-19 Survey From the Working Group of the European Society for Organ Transplantation

“…Myelotoxicity is perceived as the major drawback with current agents, underlying the need for novel therapies for prophylaxis, to facilitate a safer and more effective strategy to prevent CMV infection. In this setting, the potential availability of letermovir in SOT may represent a relevant step forward (31)(32)(33)(34)(35).…”

CMV antiviral stewardship: navigating obstacles to facilitate target attainment

“…Letermovir is a terminase inhibitor FDA approved for the prevention of CMV infection in HSCT patients. [46] Some studies describing its use in SOT exist [47,48 ▪ ] and a clinical trial in kidney transplant patients is currently underway [49]. Although this is an attractive option as it mitigates many of the problems associated with PEM and valganciclovir prophylaxis, there are several obstacles to its use.…”

Cytomegalovirus antiviral stewardship in solid organ transplant recipients: A new gold standard

“…Therefore in our stewardship program, we have moved away from traditional management with treatment to negativity followed by secondary prophylaxis, to a conversion strategy utilizing alternative, nonmyelosuppressive antivirals (letermovir, and more recently maribavir) in those that qualify for secondary prophylaxis based on risk factor screening (Table 3). With this strategy, we have seen rapid improvement in myelosuppression and CMI development even in the most refractory cases 13 . It is well known that a dual pronged approach to treatment utilizing both antiviral drugs and immunosuppressive adjustment is indicated to appropriately treat CMV disease.…”