High dose valacyclovir for cytomegalovirus prophylaxis following allogeneic hematopoietic cell transplantation

Introduction Cytomegalovirus (CMV) is one of the most common and clinically significant viral infections following allogeneic hematopoietic cell transplantation (HCT). Currently available options for CMV prophylaxis and treatment present challenges related to side effects and cost. Methods In this retrospective medical record review, the incidence of clinically significant CMV infection (CMV disease or reactivation requiring preemptive treatment) following allogeneic HCT was compared in patients receiving valacyclovir 1 g three times daily versus acyclovir 400 mg every 12 h for viral prophylaxis. Results Forty-five patients who received valacyclovir were matched based on propensity scoring to 35 patients who received acyclovir. All patients received reduced-intensity conditioning regimens containing anti-thymocyte globulin. Clinically significant CMV infection by day + 180 was lower in the valacyclovir group compared to the acyclovir group (18% vs. 57%, p = 0.0004). Patients receiving valacyclovir prophylaxis also had less severe infection evidenced by a reduction in CMV disease, lower peak CMV titers, delayed CMV reactivation, and less secondary neutropenia. Conclusion Prospective evaluation of valacyclovir 1 g three times daily for viral prophylaxis following allogeneic HCT is warranted. Due to valacyclovir's favorable toxicity profile and affordable cost, it has the potential to benefit patients on a broad scale as an option for CMV prophylaxis.

1378. Impact of Cytomegalovirus Prophylaxis on Clinical Outcomes in Kidney Transplantation: A United States Renal Data System-Medicare Linked Database Study

Background Guidelines recommends cytomegalovirus (CMV) prophylaxis by CMV serostatus/risk status, as the currently available antiviral agents may lead to myelosuppressive events in kidney transplant recipients (KTRs). Limited data exist for the United States (US) on the such clinical outcomes with CMV prophylaxis KTRs especially stratified by CMV risk strata. We examined the associations between clinical outcomes and CMV prophylaxis among adult KTRs stratified by CMV risk strata. Methods We employed a retrospective cohort design using the US Renal Data System registry-linked Medicare data (2011-2017). The cohort included 22,918 adult KTRs with continuous Medicare Part A & B coverage for ≥ 6-month pre and ≥ 12-month post KT and Part D coverage for ≥ 12-month post- KT. CMV prophylaxis was defined as ≥ 1 prescription fill or medical claim for valacyclovir or valganciclovir at prophylaxis doses within 28 days post-KT. Results CMV prophylaxis was utilized by 75% of the cohort. In no CMV prophylaxis group, 52.2% and 34.2% of high and intermediate risk KTRs received valganciclovir (as either pre-emptive or deferred therapy), respectively. Among high risk KTRs, CMV prophylaxis group had significantly lower proportions of KTRs with CMV infection, opportunistic infections (OIs) including bacterial, and fungal infections, and new onset of diabetes mellitus (NODAT) compared to no prophylaxis group. There were no differences in the rates of acute rejection or death; however, a trend towards lower rate of graft-failure at 12-month post-KT. Nearly 40% of high-risk KTRs had myelosuppressive events (leukopenia: 18%; neutropenia:15% thrombocytopenia :19%); however, their differences were non-significant except for thrombocytopenia by CMV prophylaxis status (Table 1). CMV infection and myelosuppressive event rates were higher in high-risk than intermediate/low risk KTRs irrespective of CMV prophylaxis status. Conclusion CMV prophylaxis was associated with lower rates of CMV infection, OIs, NODAT and graft failure compared to no prophylaxis, however, the burden of CMV infection, OIs and myelosuppression was greater in high-risk KTRs indicating further research is needed on factors associated with greater disease burden in high-risk KTRs. Table 1 Disclosures Amit D. Raval, PhD, Merck and Co., Inc. (Employee) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder)

1387. Impact of Cytomegalovirus Prophylaxis on Healthcare Resource Use and Costs among Kidney Transplant Recipients: A United States Renal Data System-Medicare Linked Database Study

Background Cytomegalovirus (CMV) management requires a balance between reducing the risk of CMV infection and avoiding anti-viral toxicities. Limited information is available on the impact of CMV prophylaxis on the healthcare resource use (HCRU) and costs among adult kidney transplant recipients (KTRs) in the United States. Therefore, we examined HCRU and cost associated with CMV prophylaxis stratified by the CMV risk categories among KTRs at 1-year post-KT. Methods We identified a cohort of 22,918 adults first-time KTRs during 2011–2017 using the US Renal Data System registry-linked Medicare data. Additional inclusion criteria were to have continuous coverage in Medicare Part A & B for ≥ 6-month pre- and ≥ 12-month post KT and Medicare Part D for ≥12-month post-KT. CMV prophylaxis was confirmed as ≥ 1 prescription fill for valacyclovir/(val)ganciclovir prophylaxis doses within 28 days post-KT. Results CMV prophylaxis was utilized in 86%, 82%, and 32% of high, intermediate, and low-risk KTRs with an average cost of prophylaxis per KTRs of &16,241, &9481, and &8,648, respectively. In no prophylaxis groups, valganciclovir was utilized in 52%, 34%, and 36% of KTRs (as either pre-emptive or deferred therapy) with an average cost of &6,719, &2,722, and &431 among high, intermediate, and low-risk KTRs, respectively. Among high-risk KTRs, CMV prophylaxis group had a significantly higher prescription drug cost (&26,060 vs. &13,433) but a lower average direct healthcare medical cost (&84,914 vs. &101,268), mainly due to lower all-cause hospitalization cost (&56,758 vs. &69,852) (Table 1). CMV prophylaxis group had lower rates of all-cause rehospitalization, and CMV-and opportunistic infection (OIs)-related hospitalization compared to no prophylaxis (Table 2). In high-risk KTRs, nearly 32% had myelosuppressive events-related hospitalization, and 15% filled granulocyte colony-stimulating factors with an average cost of &4,695 per treated KTR. Conclusion CMV prophylaxis had a higher cost of medications but had a lower medical cost with including all-cause and CMV-related hospitalizations. Myelosuppressive events were frequent and resource-intensive especially in high and intermediate-risk KTRs. Disclosures Amit D. Raval, PhD, Merck and Co., Inc. (Employee) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder)

Evaluation of Cytomegalovirus Infections in Liver Transplant Recipients Under Universal Prophylaxis: A Single Centre Experience

Background: Cytomegalovirus (CMV) is one of the leading viral agents that can pave the way for serious complications and organ damage in solid organ transplant (SOT) recipients after transplantation. Strategies have been developed to protect at-risk patients from CMV infection following transplantation. Since more than 90% of adults in Turkey were positive for CMV IgG, universal CMV prophylaxis was applied, and the results were evaluated. Objectives: This study aimed to evaluate the results of universal CMV prophylaxis after liver transplantation in the long term. Methods: A total of 1,090 liver transplant patients were evaluated in terms of CMV infection in the Organ Transplantation Institute of Inonu University, Malatya, Turkey, from October 2014 to December 2019. In order to identify the CMV infections, quantitative nucleic acid amplification (QNAT) was used to detect potential CMV DNA. The cut-off value of CMV DNA was determined to be 1000 copies/mL after transplantation. Results: According to the clinical and laboratory assessments, 33 (3%) patients were diagnosed with CMV infection, and 25 (2.3%) patients were evaluated as possibly having CMV syndrome. Also, eight of the 33 patients were assessed as having end-organ CMV disease and 25 as probable CMV syndrome. In the late period following prophylaxis, CMV infection was observed in 10 (0.9%) cases. The infection rate after prophylaxis (0.9%) was lower than the infection rate (2.1%) seen during prophylaxis. Conclusions: Close clinical follow-up with CMV prophylaxis and strict monitoring of CMV DNA by determining a specific cut-off point are important in the follow-up of liver transplant patients.

Letermovir Prophylaxis for Cytomegalovirus Infection in Allogeneic Stem Cell Transplantation: A Real-World Experience

Despite effective treatments, cytomegalovirus (CMV) continues to have a significant impact on morbidity and mortality in allogeneic stem cell transplant (allo-SCT) recipients. This multicenter, retrospective, cohort study aimed to evaluate the reproducibility of the safety and efficacy of commercially available letermovir for CMV prophylaxis in a real-world setting. Endpoints were rates of clinically significant CMV infection (CSCI), defined as CMV disease or CMV viremia reactivation within day +100-+168. 204 adult CMV-seropositive allo-SCT recipients from 17 Italian centres (median age 52 years) were treated with LET 240 mg/day between day 0 and day +28. Overall, 28.9% of patients underwent a haploidentical, 32.4% a matched related, and 27.5% a matched unrelated donor (MUD) transplant. 65.7% were considered at high risk of CSCI and 65.2% had a CMV seropositive donor. Low to mild severe adverse events were observed in 40.7% of patients during treatment [gastrointestinal toxicity (36.3%) and skin rash (10.3%)]. Cumulative incidence of CSCI at day +100 and day +168 was 5.4% and 18.1%, respectively, whereas the Kaplan-Meier event rate was 5.8% (95% CI: 2.4-9.1) and 23.3% (95% CI: 16.3-29.7), respectively. Overall mortality was 6.4% at day +100 and 7.3% at day +168. This real-world experience confirms the efficacy and safety of CMV.

Letermovir for Cytomegalovirus Prophylaxis in Lung Transplant Patients with Valganciclovir-Induced Leukopenia

Cytomegalovirus (CMV) prophylaxis with valganciclovir is the standard of practice in most transplant centers, but treatment-related leukopenia can limit valganciclovir’s use. Therefore, we evaluated letermovir, a novel antiviral agent recently approved for use in hematopoietic cell transplant patients as CMV prophylaxis, in lung transplant recipients unable to tolerate valganciclovir due to severe leukopenia. We performed a retrospective analysis of all lung transplant patients at our center who received letermovir for CMV prophylaxis between 1 December 2018 and 1 January 2020. A repeated measures mixed model was used to analyze white blood cell (WBC) trends, and descriptive statistics were used to analyze secondary endpoints, including CMV DNAemia, renal function, immunosuppression dosing, and allograft function. Seventeen patients were administered letermovir during the study period due to valganciclovir-induced leukopenia (median WBC nadir 1.1 K/uL, range <0.30–2.19 K/uL). Median WBC improvement was noted in 15 (88.2%) patients after starting letermovir. Breakthrough CMV DNAemia necessitating treatment occurred in two patients, with one of the two cases being due to patient noncompliance. CMV resistance to letermovir was detected in two patients, necessitating a change to an alternative agent in one of these patients. No major side effects were reported in any patient. Letermovir is a generally safe and effective alternative for CMV prophylaxis in lung transplant recipients unable to tolerate valganciclovir due to leukopenia.