Real-World Use of Letermovir and Maribavir for CMV Prophylaxis and Treatment in Solid Organ Transplant Recipients: Clinical Outcomes and Resistance Patterns From a Dual-Center Cohort.

BACKGROUND

Cytomegalovirus (CMV) is a major opportunistic infection in solid organ transplant (SOT) recipients. Although valganciclovir is first-line for CMV treatment, its use may be limited by resistance and myelotoxicity. Letermovir (LET) and maribavir (MBV) are increasingly used as alternative therapies, though real-world outcomes remain incompletely defined. This study evaluated real-world outcomes of LET and MBV in SOT recipients for whom standard CMV therapy was inadequate or not feasible. Viral clearance, breakthrough infection, refractory infection, and resistance emergence were assessed.

METHODS

We conducted a retrospective cohort analysis of adult SOT patients receiving LET (2018-2025) and/or MBV (2019-2025) at two transplant centers. Primary outcomes included CMV breakthrough (≥ 500 IU/mL) during LET prophylaxis and CMV clearance (< 200 IU/mL) at the end of MBV treatment. Secondary outcomes included resistant, refractory, and recurrent CMV infection within 3 months post-therapy.

RESULTS

Among 47 LET courses (41 patients), breakthrough CMV occurred in 14/32 (44%) secondary prophylaxis (SP) courses (median viral load [VL]: 1037 IU/mL, interquartile range [IQR] 673-3427) but in none of the 15 primary prophylaxis (PP) courses. No resistance to LET was detected during or after prophylaxis. MBV was administered in 21 courses (17 patients); MBV-refractory/resistant (R/R) infection occurred in 8 courses (38%), and 11 (52%) courses achieved CMV clearance. Within 3 months post-MBV, 14 (67%) courses had CMV VL ≥ 1000 IU/mL, and two (10%) courses experienced recurrence. MBV resistance emerged in 6/17 (35%) patients during or after treatment.

CONCLUSIONS

LET was effective for PP but associated with frequent breakthroughs in SP patients. MBV was limited by incomplete viral suppression and emergent resistance. These findings highlight the variable effectiveness of LET and MBV in clinical practice and support the need for further research to define optimal antiviral use in SP and refractory CMV treatment.