Background Cytomegalovirus (CMV) infection is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) that significantly impacts prognosis and can even be life-threatening. CMV infection increases non-relapse mortality (NRM), the incidence of graft-versus-host disease (GVHD), and secondary bacterial or fungal infections. Conventional anti-CMV drugs are associated with complications such as myelosuppression and nephrotoxicity and have limited efficacy in refractory CMV infections and CMV disease. Maribavir, a novel anti-CMV agent, exhibits multimodal anti-CMV activity without cross-resistance to ganciclovir or foscarnet. Its application in post-transplant CMV infections and its favorable safety profile warrant further investigation.

Objective This study aimed to evaluate the safety and efficacy of maribavir in treating refractory or drug-intolerant CMV viremia and CMV disease following allo-HSCT.

Methods

A retrospective analysis was conducted on the outcomes of patients with refractory CMV viremia and CMV disease who were intolerant to conventional antiviral drugs and received maribavir treatment following allo-HSCT at Yanda Ludaopei Hospital in Hebei Province from April 2024 to March 2025. Maribavir was administered when patients met any of the following criteria: ① Diagnosis of refractory CMV infection; ② Intolerance to conventional therapy: e.g., bone marrow suppression, renal dysfunction, etc. ③ Early CMV activation with newly engrafted leukocytes post-transplantation. The maribavir dosing regimen was as follows: 400 mg twice daily orally for children ≥12 years and adults; for children <12 years, the dose was referenced from https://clinicaltrials.gov/ct2/show/NCT05319353.

Results Among the 57 patients treated with Maribavir, 35 were male and 22 were female, with a median age of 30 years (range: 1–61 years). The types of diseases included: Acute myeloid leukemia (n=30), Acute lymphoblastic leukemia (n=10),Mixed-phenotype acute leukemia (n=2),Chronic myeloid leukemia (n=1),T-lymphoblastic lymphoma (n=1),Myelodysplastic syndrome (n=3),Aplastic anemia (n=7),Multiple myeloma (n=1),Primary cutaneous T-cell lymphoma(n=1),Enteropathy-associated T-cell lymphoma (n=1).Patients underwent haploidentical HSCT (Haplo-HSCT)(n=49), matched sibling donors HSCT (MSD-HSCT)(n=3), matched unrelated donors HSCT (MUD-HSCT) (n=3), autologous HSCT(Auto-HSCT)(n=1),umbilical cord blood transplantation (UCBT)(n=1).51 cases underwent a single transplant, 3 cases underwent two transplants, and 2 cases underwent three transplants. The pre-transplant CMV serostatus was as follows: 88% of patients were D+/R+ type, 11% were D-/R+ type, and 1% were D-/R- type. The conditioning regimen was Bu-based in 38 cases (66%), TBI-based in 17 cases (30%), and Mel-based in 2 cases (4%).

Fifty patients received letermovir for CMV prophylaxis. The median time to CMV viremia post-transplant was 118 days (range: 6–2619), with a median peak plasma CMV DNA level of 7,200 copies/mL (range: 1,100–820,000). Eight patients (14%) were diagnosed with CMV disease (CMV pneumonia: n=5; CMV enteritis: n=3). Prior to maribavir, 53 patients had received conventional anti-CMV therapy, with 5 developing renal injury and 6 experiencing pancytopenia. Four patients received maribavir as first-line therapy. Maribavir was initiated at a median of 6 days (range: 1–41) after CMV detection, with a median treatment duration of 10.5 days (range: 3–55). By day 7 (range: 2–22) of maribavir treatment, CMV DNA levels decreased to <1,000 copies/mL in most cases. Five patients experienced CMV rebound (>1,000 copies/mL) at a median of 9 days (range: 4–16) after discontinuation; retreatment with maribavir for a median of 21 days (range: 13–28) resulted in sustained viral clearance. Adverse events included grade 1 dysgeusia (n=4) and grade 2 myelosuppression (n=2). Five deaths occurred due to: transplant-associated thrombotic microangiopathy (TA-TMA, n=1), septic shock (n=1), CMV pneumonia (n=1), Grade IV acute GVHD (n=2). The 1-year overall survival rate was 86.5% (95% CI: 74.7%–98.4%).

Conclusion

Maribavir demonstrated high efficacy and a favorable safety profile in treating refractory or drug-intolerant CMV viremia and CMV disease post- allo HSCT, characterized by rapid viral clearance (short median time to response) and minimal adverse effects.

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2025
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