Cytomegalovirus in Allogeneic Hematopoietic Transplantation: Impact on Costs and Clinical Outcomes Using a Preemptive Strategy

Saullo, Jennifer L.; Li, Yanhong; Messina, Julia A.; Thompson, Jocelyn S.; Dalton, Tara; Giri, Vinay K.; Reed, Shelby D.; Miller, Rachel; Horwitz, Mitchell E.; Alexander, Barbara D.; Sung, Anthony D.

doi:10.1016/j.bbmt.2019.11.005

Cited by 8 publications

(7 citation statements)

References 32 publications

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“…CMV reactivation has been associated with adverse outcomes in HCT recipients, including significantly longer length of hospital stay and greater use of hematopoietic growth factors. 16 Further, in a retrospective cohort review of 926 allogeneic HCT recipients with CMV infection, higher viral loads were associated with overall and non-relapse mortality. 6 In this cohort review, the risk of death was significantly diminished by day 60 following the transplant.…”

Section: Discussionmentioning

confidence: 98%

High dose valacyclovir for cytomegalovirus prophylaxis following allogeneic hematopoietic cell transplantation

Hawks

Fegley

Sabo

et al. 2021

J Oncol Pharm Pract

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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.

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Section: Discussionmentioning

confidence: 98%

High dose valacyclovir for cytomegalovirus prophylaxis following allogeneic hematopoietic cell transplantation

Hawks

Fegley

Sabo

et al. 2021

J Oncol Pharm Pract

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“…The currently available antivirals for PET, (val)ganciclovir or foscarnet, are associated with myelosuppression or nephrotoxicity, respectively, and although uncommon, some patients still develop CMV EOD and may die of CMV or treatment-related toxicities [8]. CMV treatment is associated with increased risk for readmissions, prolonged hospitalization, and increased healthcare costs [9,10,23,24]. As safe and effective CMV prophylaxis has become available and new options for treatment of CMV are entering late stages of development, studies quantifying the impact of CMV and PET on clinical outcomes and HCRU are relevant for programmatic decision making.…”

Section: Discussionmentioning

confidence: 99%

“…CMV infection following HCT has been associated with increased economic burden in HCT recipients. Studies evaluating patient-level cost and HCRU showed increased total medical cost and longer LOS for patients receiving PET compared with patients not receiving PET [10, 24,25]. El Haddad et al [23] showed that the mean direct cost per patient admitted for PET in MD Anderson Cancer Center, was significantly higher compared to patients admitted for management of GVHD.…”

Section: 220mentioning

confidence: 99%

Impact of Preemptive Therapy for Cytomegalovirus on Hospitalizations and Cost after Hematopoietic Stem Cell Transplantation

Fang

Zavras

et al. 2020

Biology of Blood and Marrow Transplantation

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Cytomegalovirus (CMV) viremia occurs in 40% to 80% of CMV-seropositive (R+) recipients of allogeneic hematopoietic cell transplantation (HCT). The preemptive therapy (PET) strategy has reduced the risk of CMV end-organ disease (EOD) and associated mortality but may lead to substantial healthcare resource utilization (HCRU) and costs. Real-world data on the economic impact of PET is relevant for the evaluation of alternative strategies for CMV management. We examined the impact of clinically significant CMV treated with PET on inpatient length of stay (LOS), number of readmissions, and associated costs from day 0 through day 180 post-HCT. This was a retrospective study of R+ adults who underwent peripheral blood or marrow allogeneic HCT at Memorial Sloan Kettering Cancer Center between March 2013 and December 2017. Patients were routinely screened for CMV by qPCR and received PET according to institutional standards of care. Data were extracted from electronic medical records and hospital databases. Itemized cost data per patient were obtained from the Vizient database, adjusted to 2017 dollars using inflation indices. Study outcomes included HCRU evaluated by inpatient LOS and inpatient cost in patients who received PET for clinically significant CMV (PET group) compared with those who did not receive PET (no PET group) and the frequency and cost of CMV-related readmissions compared with non CMV-related readmissions. We used generalized linear models to examine the incremental HCRU and costs associated with PET controlling for other potential factors. Of 357 patients, PET was initiated in 208 (58.3%), at a median of 35 days after HCT. By day 180, 23 patients (6.4%) had developed CMV EOD and 3 (.8%) had died of CMV. Compared with the no PET group, the PET group had a longer LOS for HCT admission (P = .0276), longer total LOS by day 180 (P = .0001), a higher number of readmissions (P = .

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“…Survival data from months 0–12 post-transplant were obtained from the phase III clinical trial for letermovir [ 19 ]. Data for survival from the beginning of year 2 until year 10 were extrapolated using data from a published study in a cohort of allo-HCT recipients followed up to 5 years post-transplant [ 31 ]. Data from the Kaplan–Meier curve of the study were extracted using the ‘digitize’ package in R (Boston, MA, USA) and were used to reconstruct individual patient-level data using methods adapted from Guyot et al [ 32 , 33 ].…”

Section: Methodsmentioning

confidence: 99%

Cost Effectiveness of Letermovir for Cytomegalovirus Prophylaxis Compared with Pre-Emptive Therapy in Allogeneic Hematopoietic Stem Cell Transplant Recipients in the United States

Sepassi

Saunders

Bounthavong

et al. 2023

PharmacoEconomics Open

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Purpose The aim of this study was to assess the cost effectiveness of letermovir prophylaxis with the option for subsequent pre-emptive therapy (PET) for the prevention of cytomegalovirus (CMV) infection compared with a PET-only scenario in adult allogeneic hematopoietic stem cell transplant (allo-HCT) recipients in the United States over a 10-year time horizon. Materials and Methods A publicly available decision tree model was constructed using a commercial third-party payer perspective to simulate an allo-HCT recipient’s clinical trajectory in the first-year post-transplant, followed by entry to a Markov model to simulate years 2 through 10. Clinical inputs and utility estimates were derived from published literature. Costs were derived from published literature and US Department of Veterans Affairs Federal Supply Schedule drug pricing. Outcomes assessed included life expectancy, quality-adjusted life-years (QALYs), direct medical costs, and the incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses (PSA) were performed to test the robustness of the findings. Results Compared with PET alone, letermovir prophylaxis was projected to increase life-years per person (4.99 vs. 4.70 life-years), and increase QALYs (3.29 vs. 3.08) and costs (US$83.411 vs. US$70,698), yielding an ICER of US$59,356 per QALY gained. One-way sensitivity analyses indicated our model was sensitive to mortality (ICER: $164,771/QALY) and utility (letermovir ICER: $117,447/QALY; PET ICER: $107,290/QALY) in the first-year post-transplant. In 57.1% of the PSA simulations, letermovir was a cost-effective option using a willingness-to-pay threshold of US$100,000 per QALY. Conclusions Letermovir prophylaxis is cost effective compared with PET alone with a willingness-to-pay threshold of US$100,000 per QALY gained. Sensitivity analysis results indicate future research is required to understand the impact of mortality and quality of life in the first-year post-transplant to arrive at a conclusive decision on letermovir adoption. Supplementary Information The online version contains supplementary material available at 10.1007/s41669-023-00398-y.

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Cytomegalovirus in Allogeneic Hematopoietic Transplantation: Impact on Costs and Clinical Outcomes Using a Preemptive Strategy

Cited by 8 publications

References 32 publications

High dose valacyclovir for cytomegalovirus prophylaxis following allogeneic hematopoietic cell transplantation

High dose valacyclovir for cytomegalovirus prophylaxis following allogeneic hematopoietic cell transplantation

Impact of Preemptive Therapy for Cytomegalovirus on Hospitalizations and Cost after Hematopoietic Stem Cell Transplantation

Cost Effectiveness of Letermovir for Cytomegalovirus Prophylaxis Compared with Pre-Emptive Therapy in Allogeneic Hematopoietic Stem Cell Transplant Recipients in the United States

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