Letermovir prophylaxis through day 100 post transplant is safe and effective compared with alternative CMV prophylaxis strategies following adult cord blood and haploidentical cord blood transplantation

Sharma, Prashant; Gakhar, Neel; MacDonald, Jennifer; Abidi, Maheen Z.; Benamu, Esther; Bajrovic, Valida; Purev, Enkhtsetseg; Haverkos, Bradley M.; Tobin, Jennifer; Kaiser, Jeff; Chase, Stephanie; Miller, Matthew W.; Weinberg, Adriana; Gutman, Jonathan A.

doi:10.1038/s41409-019-0730-y

Cited by 35 publications

(38 citation statements)

References 20 publications

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“…Notably, because CMV is known to reactivate early after CBT [28], it is suggested to initiate LMV therapy on transplant day 0. No delays in engraftment or graft failure issues were observed with this approach [26].…”

Section: Real-world Experience With Lmv In Primary Prophylaxis Of CMVmentioning

confidence: 91%

“…The high-risk HCT patients had a higher benefit (22.2% vs 62.8%, p=0.004) than the low-risk group ( LMV is safe and effective compared with alternative prophylaxis approaches following CBT through day 100. No patients in the LMV group received additional CMV-directed treatment while on LMV [26].…”

Section: Real-world Experience With Lmv In Primary Prophylaxis Of CMVmentioning

confidence: 99%

“…A significant potential concern with LMV prophylaxis, particularly following CBT, is the possibility for delayed reactivation and CMV disease following discontinuation of the drug [26]. Until more robust data on this question are available, it was postulated that in patients at high risk for CMV reactivation, the prophylaxis with LMV should be continued.…”

Section: Real-world Experience With Lmv In Primary Prophylaxis Of CMVmentioning

confidence: 99%

“…Until more robust data on this question are available, it was postulated that in patients at high risk for CMV reactivation, the prophylaxis with LMV should be continued. Serial CMV monitoring at least monthly through 6 months post CBT is recommended [26].…”

Section: Real-world Experience With Lmv In Primary Prophylaxis Of CMVmentioning

confidence: 99%

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Prophylaxis vs preemptive therapy in prevention of CMV infection: new insight on prophylactic strategy after allogeneic hematopoietic cell transplantation

Styczyński

2020

Acta Haematologica Polonica

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Cytomegalovirus (CMV), the beta-human herpesvirus type 5 (HHV-5), is a major cause of morbidity in immunocompromised hosts, especially recipients of allogeneic hematopoietic cell transplantation (HCT) or solid organ transplantation. The standard-of-care approach to CMV prevention based on CMV surveillance-guided preemptive therapy is being challenged by the recent approval of letermovir (LMV) for primary prophylaxis. Real-word clinical data show dramatic improvement in the reduction of risk of CMV infection and any CMV viremia in all studies performed so far. LMV is the drug that is breaking the paradigm of preemptive therapy with shift to prophylaxis. A summary of reported data presented in 2019 annual meetings of American Society of Transplantation and Cellular Therapy (ASTCT), European Society for Blood and Marrow Transplantation (EBMT) and American Society of Hematology (ASH), as well as already published results, is presented in this review. A total number of 401 adult high-risk patients on primary prophylaxis after HCT were reported in 11 studies up to January 1, 2020. It was shown that fewer patients in the LMV arms had any CMV reactivation or need for CMV treatment compared with the any other prophylactic or preemptive approaches. In conclusion, LMV is much highly effective than CMV-guided preemptive therapy in preventing CMV infection and CMV disease. The use of LMV in prophylaxis results in an improvement in overall survival during the first 24 and 48 weeks. LMV has a favorable safety profile, as it does not cause myelotoxicity. Current guidelines of European Conference on Infections in Leukemia (ECIL7) recommend LMV for the use in prophylaxis of CMV infection in patients after allogeneic hematopoietic cell transplant.

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Section: Real-world Experience With Lmv In Primary Prophylaxis Of CMVmentioning

confidence: 91%

Section: Real-world Experience With Lmv In Primary Prophylaxis Of CMVmentioning

confidence: 99%

Section: Real-world Experience With Lmv In Primary Prophylaxis Of CMVmentioning

confidence: 99%

Section: Real-world Experience With Lmv In Primary Prophylaxis Of CMVmentioning

confidence: 99%

See 2 more Smart Citations

Prophylaxis vs preemptive therapy in prevention of CMV infection: new insight on prophylactic strategy after allogeneic hematopoietic cell transplantation

Styczyński

2020

Acta Haematologica Polonica

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“…CMV reactivation occurred in 7 patients in the letermovir group (22%) compared with 20 (33%) patients and 23 (57%) patients in the “valacyclovir day 100” and “valacyclovir to discharge” groups, respectively. No patients in the letermovir group required CMV‐directed therapy 41 …”

Section: Cytomegalovirus In Alternative Donor Transplantsmentioning

confidence: 99%

Incidence of viral and fungal complications after utilization of alternative donor sources in hematopoietic cell transplantation

et al. 2020

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Allogeneic hematopoietic cell transplantation (HCT) remains the only curable option for adult patients with hematologic malignancies. According to guidelines published by the American Society for Transplantation and Cellular Therapy, allogeneic HCT should be offered to all intermediate‐ and high‐risk patients with acute leukemia. While matched‐related donor (MRD) grafts continue to be the preferred stem cell source for allogeneic HCT, studies comparing MRD grafts to matched‐unrelated donor (MUD) grafts showed comparable outcomes in patients with acute leukemia. Unfortunately, for those without a suitable matched‐related graft, the probability of finding a suitable matched‐unrelated donor varies significantly depending on racial and ethnic background. With allogeneic HCT procedures increasing year after year due to the increased availability of suitable donors, each of these alternative donor sources merits special clinical considerations, specifically with regard to infections. Infections remain a significant cause of morbidity and mortality after allogeneic transplant, especially in those receiving alternative donor grafts. Due to the high‐risk nature associated with these donor grafts, it is important to understand the true risk of developing infectious complications. While there are a multitude of infections that have been described in patients post‐allogeneic HCT, this review seeks to focus on the incidence of cytomegalovirus (CMV) and invasive fungal infections (IFI) in adult patients receiving alternative donor source transplantation for hematologic malignancies.

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Immunovirology of cytomegalovirus infection in allogeneic stem cell transplant recipients undergoing prophylaxis with letermovir: A narrative review

Solano

Giménez

Albert

et al. 2023

Journal of Medical Virology

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On November 7, 2017, the US Food and Drug Administration approved the use of letermovir (LMV) for prophylaxis of cytomegalovirus (CMV) infection in adult CMV‐seropositive allogeneic stem cell transplant recipients. After 6 years of use, a large body of real‐world experience has been accumulated that validates the Phase III clinical trial results, in which LMV was shown to significantly reduce the risk of clinically significant CMV infection—defined as CMV end‐organ disease or CMV DNAemia requiring pre‐emptive antiviral therapy (PET)—and increase survival up to Week 24 after treatment inception. Notwithstanding, several issues still need to be settled, thus further investigation is required. First, since viral DNA may accumulate as a result of LMV‐driven abortive CMV infection, what is the optimal viral load threshold in the blood that would prompt LMV prophylaxis interruption and PET inception? Should this be adapted to the patient's risk? Second, what is the impact of LMV prophylaxis on the reconstitution of functional CMV‐specific T‐cell responses? Would it be a wise approach to individually tailor the duration of LMV treatment according to the number of peripheral blood CMV‐specific T cells at the end of regular prophylaxis? Third, how frequently do LMV‐resistant strains arise while patients are on LMV prophylaxis and how could this be minimized? Here, we discuss the literature addressing these topics.

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Letermovir prophylaxis through day 100 post transplant is safe and effective compared with alternative CMV prophylaxis strategies following adult cord blood and haploidentical cord blood transplantation

Cited by 35 publications

References 20 publications

Prophylaxis vs preemptive therapy in prevention of CMV infection: new insight on prophylactic strategy after allogeneic hematopoietic cell transplantation

Prophylaxis vs preemptive therapy in prevention of CMV infection: new insight on prophylactic strategy after allogeneic hematopoietic cell transplantation

Incidence of viral and fungal complications after utilization of alternative donor sources in hematopoietic cell transplantation

Immunovirology of cytomegalovirus infection in allogeneic stem cell transplant recipients undergoing prophylaxis with letermovir: A narrative review

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