1742. Kinetics of CMV Viremia with Letermovir Prophylaxis in the First 100 Days post Hematopoietic Cell Transplantation (HCT): A Single-center Experience

Abstract

BackgroundLetermovir (LTV) is approved for the prevention of CMV infection in CMV seropositive (R+) HCT recipients. Low rates of CMV breakthrough viremia have been reported with LTV prophylaxis. We studied the kinetics of CMV reactivation up to day (D) +100 in patients (patients) receiving LTV prophylaxis and compared them to historical controls not receiving LTV.MethodsRetrospective cohort study of CMV R+ recipients of peripheral blood or marrow allografts at MSKCC during 2017–2018. Routine LTV prophylaxis was implemented in MSKCC in December 2017. Patients were categorized based on LTV prophylaxis to LTV group (LTV prophylaxis) and no LTV group [managed with preemptive therapy (PET)]. Routine CMV monitoring was performed weekly by a qPCR assay in plasma from D +14 through D +100. CMV viremia was defined as any detectable CMV viral load (VL). Clinically significant CMV viremia (csCMV) was defined as any CMV VL treated preemptively. CMV end-organ disease (EOD) was assessed by standard criteria. LTV resistance was tested at Viracor-Eurofins Laboratories after May 2018.ResultsOf 193 R+ HCT, 98 (50.8%) were in the LTV and 95 (49.2%) in the no LTV group. CMV viremia occurred in 43 (43.9%) patients in LTV and 63 (66.3%) in no LTV (Figure 1). CMV viremia occurred earlier in LTV compared with no LTV (median, 19 vs. 26 days post HCT, respectively, P = 0.009). The duration of CMV viremia was shorter in LTV compared with no LTV (median 16 days vs. 35 days, respectively; P < 0.0001). The peak CMV VL was lower in LTV compared with no LTV (median, 137 IU/mL vs. 578 IU/mL, respectively); P < 0.0001. Rates of csCMV viremia were significantly lower in LTV compared with no LTV (5.1% vs. 54%, respectively); P < 0.0001 (Figure 2). LTV group received a total of 134 PET-days and no LTV group received 2,160 PET-days by D +100. No patient in LTV developed CMV EOD, while two patients in no LTV developed CMV duodenitis. LTV resistance was documented in 2 patients (2% of the LTV group). Overall survival by D +100 was similar between LTV and no LTV groups.ConclusionImplementation of LTV prophylaxis significantly reduced rates of csCMV infection and resulted in 93.8% reduction in total PET days. Among patients with csCMV viremia, LTV group had a shorter duration of viremia and lower peak CMV VL compared with no LTV. Disclosures All authors: No reported disclosures.