Reducing Post-Letermovir CMV Infection: Efficacy of an Immune-Reconstitution-Based Scoring System to Guide Prophylaxis Duration

Evaluation of the Efficacy of a Cytomegalovirus-Specific Immune Reconstitution-Incorporated Scoring System in Guiding the Duration of Antiviral Prophylaxis to Reduce Cytomegalovirus Infection Following Letermovir Discontinuation

With the increasing use of letermovir and considering that haploidentical hematopoietic stem cell transplantation (haplo-HSCT) predominates in China alongside a high CMV seroprevalence in the population, multiple domestic centers have reported cases of CMV infection after letermovir discontinuation. Currently, there is no clear definition for the high-risk population who may benefit from extended letermovir prophylaxis. This study aims to utilize CMV-specific immune reconstitution to identify high-risk individuals for CMV infection after letermovir cessation post-transplant, thereby guiding the timing of letermovir discontinuation and balancing the risks and safety associated with prolonged prophylaxis.

Study Overview

• Status: Not yet recruiting
• Conditions: CMV Infection

Detailed Description

Based on the established scoring system for cytomegalovirus-specific immune reconstitution, guide the discontinuation of letermovir after transplantation to reduce the incidence of CMV infection within one year after letermovir discontinuation.

• Study Type: Observational
• Enrollment (Estimated): 1114

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

For enrolled subjects, at 3 months after transplantation, apply a predictive model incorporating CMV-specific immune reconstitution to evaluate the risk of CMV infection after discontinuation of letermovir. Based on the prediction results, define low-risk, intermediate-risk, and high-risk categories. For low-risk patients, direct discontinuation of letermovir is recommended; for intermediate-risk patients, discontinuation may be considered, but close monitoring of peripheral blood CMV-DNA is required after discontinuation; for high-risk patients, extending letermovir treatment until 200 days after transplantation is recommended.

Description

Inclusion Criteria:

• (1) Recipients who meet either of the following conditions:

  1. CMV IgG-positive recipients undergoing HLA-haploidentical hematopoietic stem cell transplantation (HSCT).
  2. CMV IgG-negative recipients receiving a graft from a CMV IgG-positive donor, and who have received letermovir as CMV prophylaxis post-transplant without prior discontinuation.
• (2) Plasma CMV-DNA level below the lower limit of detection (local threshold: 400 copies/mL) within 5 days before enrollment.
• (3) Age ≥ 18 years.
• (4) Ability to provide written informed consent independently.
• (5) Negative for HIV, HBV, and HCV.
• (6) Written informed consent must be provided before initiation of any study procedure. Consent may be provided by the patient or a legally authorized representative if, in the investigator's judgment, obtaining consent directly from the patient is not in the patient's best medical interest.

Exclusion Criteria:

• (1) Prior clinical diagnosis of CMV infection, CMV disease, or CMV viremia before enrollment;
• (2) Received ganciclovir, valganciclovir, foscarnet, acyclovir (oral dose >3200 mg daily, or intravenous dose >25 mg/kg daily), valacyclovir (oral dose >3000 mg daily), or famciclovir (oral dose >1500 mg daily) within 7 days before enrollment;
• (3) Received the following treatments within 30 days before enrollment: cidofovir, CMV hyperimmune globulin, any experimental anti-CMV therapy or biologics;
• (4) Presence of uncontrolled infection, requirement for mechanical ventilation, or hemodynamic instability at enrollment;
• (5) Suffering from mental illness or other conditions that prevent compliance with study treatment and monitoring requirements;
• (6) Inability or unwillingness to sign the informed consent form;
• (7) Other special circumstances deemed ineligible by the investigator.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

CMV high risk patients after transplantation; For enrolled subjects, at 3 months after transplantation, apply a predictive model incorporating CMV-specific immune reconstitution to evaluate the risk of CMV infection after discontinuation of letermovir. Based on the prediction results, define low-risk, intermediate-risk, and high-risk categories. For low-risk patients, direct discontinuation of letermovir is recommended; for intermediate-risk patients, discontinuation may be considered, but close monitoring of peripheral blood CMV-DNA is required after discontinuation; for high-risk patients, extending letermovir treatment until 200 days after transplantation is recommended.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
incidence of CMV reactivation and cs CMV infection	one year after letermovir discontinuation

Secondary Outcome Measures

Outcome Measure	Time Frame
All-cause mortality	one year
treatment-related mortality	one year
Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	one year

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): March 14, 2026
• Primary Completion (Estimated): December 14, 2027
• Study Completion (Estimated): December 14, 2027

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: February 27, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections
• Other Study ID Numbers: IIT2025141

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No