Use of Maribavir for Multidrug Resistant Cytomegaloviremia in a Pediatric Oncology Patient

Design

Case presentation

A 2024 case report described the use of maribavir in a 4-year-old boy with standard-risk B-cell acute lymphoblastic lymphoma who developed refractory and multidrug-resistant cytomegalovirus (CMV) viremia during maintenance chemotherapy. Following an initial febrile illness upon returning from Honduras, laboratory testing revealed a CMV blood viral load exceeding 1,000,000 copies/mL. Intravenous (IV) ganciclovir was initiated, leading to symptom resolution and a decrease in viral load. However, persistent myelosuppression necessitated discontinuation of antiviral therapy after 18 days. CMV viremia later rebounded, requiring multiple sequential antiviral regimens, including valganciclovir, foscarnet, and cidofovir, each with variable efficacy and substantial adverse effects, particularly neutropenia. Despite dose adjustments, CMV viral load remained persistently elevated, and antiviral resistance testing on day 227 of therapy detected a UL54 mutation, conferring resistance to ganciclovir and foscarnet. Given the inability to fully suppress viral replication and continued chemotherapy-limiting neutropenia, maribavir was introduced at 200 mg every 8 hours. Maribavir initially demonstrated virologic response, with CMV viral load reaching a nadir of 198 copies/mL by day 394 of therapy. However, viral suppression was incomplete, and resistance to maribavir emerged by day 527, as confirmed by UL97 mutations, leading to treatment failure. Despite dose escalation to 1000 mg/day, viral load continued to rise, prompting reinitiation of valganciclovir, which coincided with restored susceptibility to ganciclovir and foscarnet. While maribavir prevented severe myelosuppression, its antiviral activity was ultimately insufficient to maintain long-term suppression, and resistance developed within approximately seven months of therapy. 

Study Author Conclusions

To our knowledge, this case is the first reported case of maribavir use for the treatment of refractory-resistant CMV viremia in a pediatric patient. Continued antiviral development and testing are needed for children with hematologic malignancies and other conditions where resistant CMV poses a threat to health. Additional studies are needed to determine appropriate concentration dosing and pharmacokinetics in pediatric patients, as appropriate dosing is not currently known. Serum maribavir levels were not obtained in our patient, but serum concentration monitoring should be investigated in the future. It is possible that the doses that we selected were sub-therapeutic. 

Maribavir use in Pediatric Immunocompromised Hosts: A Case Series to Talk about Real-world Experience

Design

Case presentation 1

An 11-year-old male patient who received a renal transplant 2 months prior and was currently receiving immunosuppression had a peak cytomegalovirus (CMV) DNA-emia level of 562,157 copies/mL. The patient presented with fever, malaise, and elevated liver function tests (LFTs). However, resistance testing was negative. The patient had previously received valganciclovir, and intravenous ganciclovir for induction therapy during peak CMV DNA-emia, followed by maribavir. Maribavir was continued until undetectable levels were observed for 4.2 weeks. The patient experienced no side effects. 

Case presentation 2

A 14-month-old male patient with severe combined immunodeficiency (SCID) who received two hematopoietic stem cell transplants (HSCTs), with the most recent one being two months prior, was currently receiving immunosuppression. The patient was found to have CMV disease in the left eye with retinitis. His peak CMV DNA-emia level was 1,198,212 copied/mL. Resistance testing found a UL 54 mutation conferring resistance to cidofovir, foscarnet, and ganciclovir. He had previously received foscarnet, letermovir, valganciclovir, and ganciclovir. However, both maribavir and letermovir were continued until CMV levels were undetectable; maribavir was stopped after 5.5 weeks. The patient was also given intravitreal foscarnet and systemic letermovir for central nervous system (CNS)/ocular penetration. Maribavir was given for CMV resistance (as maribavir has poor CNS penetration). No side effects to maribavir occurred.

Study Author Conclusions

This is the first case series describing the use of maribavir in a pediatric population. In this small cohort, maribavir was effective and well-tolerated. Further studies are needed to better CMV care in children with immunocompromised conditions.