Comparing the Efficacy of Different Durations of Maribavir Treatment Regimens in Allo-HSCT

Comparing the Efficacy of Different Durations of Maribavir Treatment Regimens in Patients With Refractory Cytomegalovirus Infection Following Allo-HSCT: a Prospective, Multicenter, Randomized, Controlled Clinical Trial

To comparing the efficacy of different durations of Maribavir treatment regimens in patients suffering from refractory CMV infection after allo-HSCT.

Hematopoietic stem cell transplantation (HSCT) represents the only potentially curative modality for hematologic malignancies. Nevertheless, post-transplant infections substantially elevate the risk of transplant-related mortality, with cytomegalovirus (CMV) infection being among the most prevalent complications. Although advances in prophylactic strategies and preemptive antiviral therapy have contributed to a measurable reduction in both the incidence of CMV infection and CMV disease, refractory or drug-resistant (R/R) CMV infection following HSCT remains a significant global therapeutic challenge. Recent epidemiologic data indicate that the incidence of drug-resistant CMV infection in HSCT recipients ranges from 1.7% to 14.5%, while that of refractory CMV infection falls between 29% and 39%. Notably, in China, the incidence of refractory CMV infection after HSCT is slightly higher than the global average-approximately 47% . Therefore, the investigator conduct a multicenter, randomized, controlled study based on retrospective research to further explore the efficacy of different durations of Maribavir treatment regimens in Allo-HSCT.

Inclusion Criteria:

1. First allogeneic hematopoietic stem cell transplantation;

2. Age ≥ 18 years;

3. Confirmed refractory CMV infection;

   Refractory CMV infection is defined as fulfillment of any one of the following criteria:

   • Persistent or increasing CMV viremia despite ≥2 weeks of appropriate antiviral therapy-specifically, CMV DNA levels remain unchanged (i.e., change ≤ log₁₀) or increase (i.e., change > log₁₀)-concomitant with lack of clinical improvement or ongoing disease progression;
   • Drug-resistant CMV infection-defined as detection of specific CMV gene mutations associated with reduced susceptibility to one or more anti-CMV agents, in patients who otherwise meet the criteria for refractory CMV infection;
   • Intolerance to anti-CMV therapy-defined as inability to continue antiviral treatment due to severe adverse effects, such as clinically significant bone marrow suppression or renal impairment;

4. Provision of written informed consent and willingness to participate in this clinical study.

Exclusion Criteria:

1. Known allergic constitution, particularly hypersensitivity to any component of maribavir;
2. Active hepatitis B infection, defined as HBV DNA level ≥ 1 × 10³ IU/mL;
3. Confirmed HIV infection;
4. Severe impairment of major organ function, including but not limited to respiratory failure, cardiac failure, decompensated hepatic insufficiency, or renal insufficiency;
5. Central nervous system CMV infection;
6. History of substance use disorder or chronic alcoholism that may compromise the validity or interpretation of trial outcomes;
7. Presence of a psychiatric disorder or cognitive impairment precluding the provision of informed consent;
8. Any other condition deemed by the investigator to render the participant unsuitable for enrollment in this clinical trial.