Efficacy and Pharmacoeconomic Impact of Letermovir for CMV Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients

Abstract

Cytomegalovirus (CMV) seropositivity and early CMV reactivation after hematopoietic-cell transplantation (HCT) remain associated with increased mortality. Those at high risk include CMV seropositive recipient/donor pairs (CMV R+ or D+) and those on escalated immunosuppression (prednisone ≥ 20mg/kg) for graft versus host disease (GVHD). Historically, our institutional CMV reactivation rate (RR) was 63% in our high risk cohort, similar to national average. Prophylaxis with letermovir, a new CMV-antiviral therapy, significantly reduced the incidence of CMV reactivation and viremia in a prospective trial (Marty FM, et al. NEJM 2017). The purpose of this study was to assess CMV reactivation, defined as CMV viral load > 500 IU/mL, with letermovir prophylaxis and its pharmacoeconomic impact in an outpatient transplant program. This was a retrospective review of adult HCT patients receiving letermovir from December 2017-August 2018 at Vanderbilt University Medical Center. Use of letermovir was standardized at a program level. Therapy was used in high risk patients, undergoing HCT with matched-unrelated donor (MUD), cord blood donor or haploidentical donor transplants with no active CMV reactivation prior to initiation and no anti-CMV treatment post-HCT. Primary endpoint compared CMV RR to historical controls utilizing a two-sided t-test. Secondary outcomes evaluated logistics and cost impact. 30 patients met entry criteria (26 CMV R+, 21 D+), RR was significantly lower than our historical control (20% vs 63%; p = 0.0003). Median time to reactivation was 38 days post-HCT (29-58). 4 of the 6 patients with reactivation received induction therapy with ganciclovir (50%), valganciclovir (25%), or letermovir (25%, peak viral load 740 IU/mL) for ∼40 days (31-52). All were CMV R-/D+ with AML and received HCT from MUD (75%) or haploidentical donors (25%). The remaining 2 patients (CMV R+/D+) had low level reactivation (137-500 IU/mL) and continued letermovir through day 100 without additional CMV treatment. Patients started letermovir by day 14 post-HCT (5-65) with a median 83 days (7-158) of prophylaxis. 3 patients received letermovir as secondary prophylaxis due to prior CMV reactivation or escalated immunosuppression for GVHD. Of those patients, reactivation occurred in 1 patient (AML MUD transplant; CMV D-/R+) who had 2 reactivations while on foscarnet therapy. No letermovir resistance was observed. Letermovir copay was between $10 and $360/month. 76% of prescriptions required prior authorization, 19% monetary grant, 18% patient assistance. Majority had private insurance (49%) and Medicare/Medicaid (36%) with a median of 3 days for approval and 5 days from prescription submission to patient medication pick-up. Primary prophylaxis with letermovir is associated with significantly lower RR compared to historical controls and is financially feasible with dedicated pharmacy services.