CMV Infection, Hematopoietic Stem Cell Transplantation
Conditions
Keywords
Letermovir; Cytomegalovirus Infection; Haploidentical HSCT
Brief summary
In the 30 years of fighting CMV infection, the mortality rate among HSCT patients has significantly reduced. Now, the focus is on improving the prognosis of HSCT patients and preventing CMV infection. The emergence of letermovir has provided a new opportunity in this regard. Letermovir, the only drug approved for CMV infection prevention in HSCT patients, works by inhibiting the CMV DNA terminase complex. Phase III studies have shown that letermovir significantly reduces CMV infection and all-cause mortality after HSCT, without increasing myelosuppression or nephrotoxicity. Real-world studies have further confirmed its efficacy in reducing CMV infection rates and antiviral use. Letermovir's global success has not yet been fully realized in China, where it is still in its early stages of use.
Detailed description
Letermovir achieved excellent therapeutic outcomes globally but is still developing in China. It received an implied license for clinical trials in June 2020, followed by marketing applications in November 2020. In December 2021, it was approved by the China National Medical Products Administration (NMPA) for preventing CMV infection and disease in CMV seropositive adult recipients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Letermovir's commercial launch in China is expected in August 2022. Given that over 90% of the Chinese population is CMV seropositive, determining whether CMV prevention is necessary based solely on serology is insufficient. The growing use of haploidentical stem cell transplantation (haplo-SCT) in China, particularly using the Beijing protocol for GVHD prevention, increases CMV risk. However, limited data exists on the efficacy of CMV prophylaxis for haplo-SCT patients in China. A real-life study assessing the efficacy, resistance, and tolerability of letermovir in this patient group is essential to guide CMV management strategies, particularly for high-risk CMV R+ haploidentical transplant recipients. This prospective study aims to evaluate letermovir's real-life impact on efficacy, resistance, tolerability, and CMV-related morbidity and mortality in China.
Interventions
DRUGLetermovir
Letermovir has achieved excellent therapeutic benefits globally but is still in its infancy in China. Letermovir obtained an implied license for a clinical trial in June 2020, and in November 2020, Letermovir submitted and accepted four new drug marketing applications in China, including injection and tablet formulations. On December 31, 2021, the China National Medical Products Administration (NMPA) approved letermovir for cytomegalovirus (CMV) seropositive adult recipients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) \[R+\] prevention of cytomegalovirus infection and cytomegalovirus disease. The commercial launch of letermovir is estimated to be in August 2022.
Sponsors
Merck Sharp & Dohme LLC
The First Affiliated Hospital of Soochow University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Haplo-SCT candidate (adult) who has decided to primary transplant and is willing to participate in the study. * The haplo-SCT candidate (adult) should be CMV seropositive recipients.
Exclusion criteria
* CMV-seronegative patient receiving a negative CMV donor graft. * Patients having active CMV DNAemia at the time of letermovir initiation. * Patient having signed the informed consent but not grafted. * Patient recruited in a clinical study on an anti-CMV trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of clinically significant CMV infection | at Week 14 following haplo-SCT | Defined as CMV DNAemia leading to preemptive treatment or presence of CMV disease using classificatory criteria published by the Disease Definitions Working Group of the Cytomegalovirus Drug Development Forum. CMV DNA threshold for initiation of preemptive therapy at our center is viral load \>500 copies/mL or above on two consecutive tests. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of CMV DNAemia and CMV disease | through Week 14 and Week 24 following haplo-SCT | CMV DNAemia refers to the presence of CMV DNA in the blood. CMV disease refers to the organ dysfunction caused by an active CMV infection, such as the lungs, liver, and retina. |
| Incidence of the resistant or refractory CMV infection | through Week 24 following haplo-SCT | Resistant or refractory CMV infection occurs if CMV levels rise by 1 log after 2 weeks of treatment or remain positive after 4 weeks. |
| Incidence of serious adverse event leading to interruption of treatment | through Week 24 following haplo-SCT | Serious adverse events refers to events that require stopping the treatment to ensure patient safety. |
| Incidence of clinically significant CMV infection | through Week 24 following haplo-SCT | Defined as CMV DNAemia leading to preemptive treatment or presence of CMV disease using classificatory criteria published by the Disease Definitions Working Group of the Cytomegalovirus Drug Development Forum. CMV DNA threshold for initiation of preemptive therapy at our center is viral load \>500 copies/mL or above on two consecutive tests. |
| Incidence of all-cause mortality and non-relapse mortality | through Week 24 following haplo-SCT | All-cause mortality refers to deaths from any cause, while non-relapse mortality refers to deaths caused by factors other than the recurrence or relapse of the original disease or condition. |
| Incidence of CMV-associated morbidity | through Week 24 following haplo-SCT | CMV-associated morbidity refers to organ damage, delay engraftment, acute or chronic GVHD occurrence, or other infectious diseases caused by CMV. |
| Incidence of rehospitalization | through Week 14, Week 24 following haplo-HSCT | The frequency or rate at which patients are readmitted to the hospital within a specified period following their discharge. |
| Incidence of CMV-related disease mortality | through Week 24 following haplo-SCT | Death resulting directly or indirectly from complications of a CMV infection, often involving severe organ damage in the lungs, liver, or other organs. |
Countries
China
Outcome results
None listed