B386 - A Single-Center, Open-Label Pilot Study Comparing De Novo Letermovir versus Valganciclovir for Cytomegalovirus Prophylaxis in African American Kidney Transplant Recipients

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Author Block: I. Yakubu, G. Abebe, D. Kumar, A. Brown, I. Moinuddin, M. Morales, S. Sterling, A. T. Iaria, B. Agegnehu, R. Marks, T. Sprague, M. Saeed, G. Gupta, Virginia Commonwealth University Health System, Richmond, VA
*Purpose: Valganciclovir (VGC) is the standard for cytomegalovirus (CMV) prophylaxis but if often limited by its myelosuppressive effects, which complicates immunosuppression management particularly in African American (AA) patients who generally require more intense immunosuppression. Letermovir (LET), offers CMV prevention without myelosuppressive effects, but data in AA kidney transplant recipients (KTR) remain scarce. We previously presented the preliminary results of our prospective single-arm trial (NCT06001320) comparing LET versus a historical VGC cohort in CMV high-risk (D+/R-) AA KTRs. Herein, we report our expanded experience with more patients and longer follow up.
*Methods: This single-center open-label pilot study excluded re-transplants, cPRA ≥ 80%, positive crossmatch, pregnancy or breastfeeding, prisoners, or hypersensitivity to study drugs. LET recipients were matched (1:1) to a historical VGC cohort based on race, age, sex, dialysis vintage, and transplant type. The primary endpoint was CMV viremia or symptomatic disease within a year. Secondary outcomes included leukopenia, acute rejection, breakthrough CMV, mycophenolate adjustments, donor-specific antibodies, and tolerability. This was an investigator-initiated trial fully supported by Merck. CMV CMI was supported by Viracor-Eurofins.
*Results: Thirty LET patients were matched to 30 VGC controls (P=NS). Median follow-up was 358 days (range: 83-365) for LET vs. 365 days (134-365) for VGC (P <0.0001). CMV viremia occurred in 7 (23.3%) LET vs. 12 (40.0%) VGC patients (P=0.1688), with significantly lower breakthrough CMV in LET (1 [3.3%] vs. 7 [23.3%] with VGC; P=0.0238). Leukopenia was markedly reduced with LET (1 [3.3%] vs. 15 [50%] with VGC; P=0.001) and G-CSF was required only in VGC patients (3 [10%] vs. 0 with LET; P=0.0780). No biopsy proven acute rejection in LET (0%) compared with 4(13.3%) in VGC (P=0.0401). One-year patient/graft survival was similar (93.3% LET vs. 96.7% VGC, P=0.5569). Two LET patients died; one from sepsis due to surgical wound complications, and the other from presumed cardiac causes, post-prophylaxis. One LET patient discontinued the drug due to rash, although improved while remaining on LET. Both CD4 and CD8 CMV-specific T-cell responses remained consistently low across all time points, showing only minimal upward trends over the first post-transplant year. Most patients were CYP3A5 expressers, with 24 (80%) carrying at least one *1 allele—including 7 homozygous *1/*1 expressors—while 6 (20%) were non-expressers.
*Conclusions: This follow up results further confirms that LET is an effective, well-tolerated alternative to VGC for CMV prophylaxis in high-risk AA KTRs. LET was associated lower breakthrough CMV and leukopenia while maintaining comparable survival.