​Litemovir helps clinical practice, and CMV management ushered in a new pattern

Introduction Cytomegalovirus (CMV) infection is a common, life-threatening, and even life-threatening complication after allogeneic hematopoietic stem cell transplantation [1]
.

Preemptive therapy is currently the standard strategy for dealing with CMV infection and CMV organ disease [2]
.

However, the occurrence of multidrug resistance and relapsed/refractory CMV infection still seriously affect the prognosis of allogeneic hematopoietic stem cell transplant recipients, which is an urgent problem to be solved in this therapy [1,2]
.

In early 2022, Merck's novel non-nucleoside CMV inhibitor, Premin® (Letermovir Tablets), was approved by the National Medical Products Administration (NMPA) for use in CMV seropositive adult recipients undergoing allogeneic hematopoietic stem cell transplantation [R+] Prevention of cytomegalovirus infection and cytomegalovirus disease [3]
.

Professor Zhao Weili, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, said: "The entry of Temovir into China has not only filled the gap in the field of cytomegalovirus prevention in the past 20 years, redefines the management of cytomegalovirus, but also strengthened active prevention.
The operability of a concept
.

" Actively prevent CMV and reduce the clinical burden of patients CMV infection is a common complication after allogeneic hematopoietic stem cell transplantation [1]
.

When faced with CMV infection, allogeneic hematopoietic stem cell transplant recipients face a huge risk of complications and death [2]
.

The current standard treatment strategy for CMV infection is preemptive treatment, but this strategy has many limitations, such as inconsistent treatment thresholds, adverse reactions such as myelosuppression and nephrotoxicity, and risks of cross-resistance, etc.
, which lead to persistent infection after transplantation.
The proportion of CMV infection and the mortality rate remain high, the medical burden of patients is heavy, and new anti-CMV infection drugs and new coping methods are urgently needed in clinical practice [1]
.

Letermovir is a specific anti-CMV drug and has no cross-resistance with traditional anti-CMV drugs such as ganciclovir [1]
.

Its pivotal phase III clinical study showed that the rate of clinically meaningful CMV infection at 24 weeks after transplantation was 18.
9% in the letermovir group and 44.
3% in the placebo group [4], and the letermovir group was compared with placebo.
The rate of group decline was 57.
3%
.

All-cause mortality at 24 weeks after transplantation was 10.
2% and 15.
9% in the two groups, respectively [5], and the rate of reduction in the letermovir group compared with the placebo group was 35.
8%
.

At the same time, in terms of safety, the adverse reactions and severity of Letermovir are similar to those of placebo [5]
.

Letermovir significantly reduces the incidence of CMV disease and the rate of CMV relapse after allogeneic hematopoietic stem cell transplantation, which has been validated by multiple real-world studies [6,7,8]
.

In addition, the study found that post-transplant temovir prophylaxis significantly reduced CMV end-organ disease, refractory or drug-resistant CMV infection, and rehospitalization in transplant recipients, delayed the median time to start preemptive therapy, and shortened anti-CMV The duration of preemptive therapy improves overall survival of transplant recipients and reduces CMV-related management and treatment costs [6,7,9,10]
.

Regarding the outstanding performance of letemovir in reducing medical risks in key clinical studies and real-world studies, Professor Zhao Weili said: "Latemovir, as the first-line drug for the prevention of cytomegalovirus in the world, can help reduce the reduction of allogeneic hematopoietic stem cells.
The treatment and economic burden of transplant patients
.

"Looking forward to improving accessibility, innovating and leading the practice of CMV, the management model of Temovir prophylactic administration not only provides strong support for the success of hematopoietic stem cell transplantation, but also provides protection against this virus.
The control port is moved from passive treatment to front-end active preventive treatment, and innovatively leads the concept of CMV preventive treatment
.

Litemovir's outstanding performance in reducing CMV-related medical risks and CMV-related treatment and management costs after allogeneic hematopoietic stem cell transplantation in international real-world data is believed to provide effective treatment for recipients after allogeneic hematopoietic stem cell transplantation in China.
Protecting and reducing the disease and economic burden of patients, at the same time, reducing the occupation of medical resources and the burden on doctors' shoulders, allowing doctors to have more energy to break through various challenges in the field of blood transplantation, and promote the level of hematopoietic stem cell transplantation in China to a new level
.

Letermovir has a very low incidence of adverse reactions such as myelosuppression and nephrotoxicity, and has no cross-resistance with traditional anti-CMV drugs such as ganciclovir [1].
These characteristics greatly facilitate its clinical application
.

In addition, in addition to the tablets approved in China, letermovir also has injection formulations in foreign countries [4]
.

This dosage form can help allogeneic hematopoietic stem cell transplant recipients who are intolerant to oral drugs to improve the efficiency of drug absorption [3]
.

If it is launched in China in the future, the two formulations will cooperate with each other, which will better meet the individualized treatment needs of patients, and is expected to further improve the effect of clinical CMV management
.

Professor Zhao Weili also said: "I hope this new drug can be more widely used in the future, and will receive more support in terms of medical insurance and accessibility, helping more patients to benefit from cutting-edge medical results
.

"References: [1] Chen Juan, Feng Sizhou.
Research status of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation [J].
International Journal of Blood Transfusion and Hematology, 2020, 43(5): 374-382.
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3760 /cma.
j.
cn511693-20200520-00107.
[2]Lin A, Maloy M, Su Y, et al.
Letermovir for primary and secondary cytomegalovirus prevention in allogeneic hematopoietic cell transplant recipients: real world experience[J].
Transplant Infectious Disease , 2019.
[3]https:// -databases/drug-trials-snapshots-prevymis.
[5]Marty FM, Ljungman P, Chemaly RF, et al.
Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation[J].
N Engl J Med.
2017,377(25) :2433–2444.
[6]Malagola M, Pollara C, Polverelli N, et al.
Advances in CMV Management: A Single Center Real-Life Experience[J].
Front Cell Dev Biol.
2020 Oct 27;8:534268.
doi : 10.
3389/fcell.
2020.
534268.
PMID: 33195184.
[7]Mori Y, Jinnouchi F, Takenaka K, et al.
Efficacy of prophylactic letermovir for cytomegalovirus reactivation in hematopoietic cell transplantation: a multicenter real-world data[J].
Bone marrow transplantation, 2020:1-10 .
[8]Bcidp A, Raja M, Morris MI, et al.
Clinical "Real-World" Experience with Letermovir for Prevention of Cytomegalovirus Infection in Allogeneic Hematopoietic Cell Transplant Recipients - ScienceDirect[J].
Biology of Blood and Marrow Transplantation, 2020 , 26(3).
[9]Joseph S, Fareed K, Lynn ST, et al.
Refractory and Resistant Cytomegalovirus After Hematopoietic Cell Transplant in the Letermovir Primary Prophylaxis Era[J].
Clinical Infectious Diseases, 2021(8):8.
[10] Royston L, Royston E, Masouridilevrat S, et al.
Letermovir Primary Prophylaxis in High-Risk Hematopoietic Cell Transplant Recipients:A Matched Cohort Study[J].
Vaccines, 2021.
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