Maribavir in stem cell transplant recipients: the registry catches up with the licence

Design

multicentre retrospective registry study across 37 EBMT centres in 15 countries, minimum 12 weeks follow-up, no comparator arm

Population

118 haematopoietic cell transplant recipients (109 adults, 9 children) receiving 126 maribavir courses, 80% as second or third line

Primary outcome

response to maribavir at 12 weeks — CMV resolution or treatment failure

Effect

resolution in 88/109 pre-emptive courses (81%) and 12/17 for CMV disease (71%); discontinuation for adverse events 2/126 (2%); 12-week survival 82% (95% CI 75-89)

Maribavir was licensed by the European Medicines Agency in 2022 for refractory or resistant cytomegalovirus after transplantation, on evidence that was thin in the haematopoietic cell transplant population specifically. This EBMT registry collected 126 courses in 118 patients — 109 adults and nine children — across 37 centres in 15 countries, all with at least 12 weeks of follow-up.

How it was actually used is as informative as how it worked. Only about half the courses (64 of 126) were for refractory or resistant infection; the other half were driven by toxicity of the alternatives, most often neutropenia in 31 courses. Eighty per cent were second or third line. CMV resolved in 88 of 109 pre-emptive courses (81%) and 12 of 17 courses given for CMV disease (71%). Discontinuation for adverse events was rare, at 2 of 126 courses. At 12 weeks overall survival was 82% (95% CI 75 to 89) and non-relapse mortality 15% (95% CI 9 to 22).

This is a retrospective registry with no comparator, so the resolution rates cannot be attributed to maribavir with confidence — patients also received other care, and centres that report to a registry are not a random sample. What it does establish is tolerability in a heavily pretreated population, and it documents a real off-label-adjacent pattern: the drug is being reached for as much to escape ganciclovir-related myelosuppression as for resistance. Anyone writing a local CMV pathway should recognise that as the actual clinical question.

• Consider maribavir where myelosuppression rather than resistance is the barrier — that was half of real-world use
• Expect roughly four in five pre-emptive courses to clear CMV, on uncontrolled data
• Confirm genotypic resistance where the indication is refractory disease, so the switch is documented
• Watch for CMV disease developing despite pre-emptive treatment — it occurred in 5% here
• Check current CDSCO approval status and cost before building maribavir into an Indian transplant pathway; this study is European

The statistics, in plain English

These are single-arm proportions with no control group, so 81% resolution is a description of what happened, not a measure of what maribavir added — some of those infections would have cleared on other treatment or immune reconstitution. Confidence intervals around the survival figures (82%, 95% CI 75 to 89) reflect sampling uncertainty only, and do not account for which centres chose to report. Retrospective registries also tend to capture patients who survived long enough to be entered, which flatters outcomes.

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