D165 - Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients: A Real World Analysis from a Single Center

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Author Block: M. Jorgenson¹, J. Descourouez¹, G. Leverson², W. Rose², A. Beyer³, D. Al-Adra², ¹UW Health, Madison, WI, ²University of Wisconsin, Madison, WI, ³Merck & Co. Inc., Rahway, NJ
*Purpose: Current US and international CMV prevention guidelines in high-risk kidney transplant (KT) recipients recommend 6 months of prophylaxis. The purpose of this study is to compare the real-world effectiveness of letermovir (LET) to valganciclovir (VGCV) and to describe HCRU and transplant related outcomes from a cohort of KT recipients at UW Health.
*Methods: Adult CMV seronegative recipients of donor CMV positive (D+/R-) KT recipients between 6/6/2021 and 6/6/2024 were evaluated as part of an interim analysis of an ongoing retrospective cohort study. Cohort (VGCV or LET) was determined based on de novo antiviral prophylaxis regimen. The primary objectives were to compare effectiveness and HCRU. Effectiveness was measured by comparing the proportion of patients who do not experience prophylaxis failure, defined as breakthrough CMV replication while receiving prophylaxis, CMV end organ disease or discontinuation due to tolerability. Additional clinical and transplant-related outcomes were also evaluated.
*Results: 105 patients met inclusion criteria: 67 patients in VGCV cohort and 38 patients in LET cohort (Table 1). The majority of patients were male recipients of a deceased donor KT with lymphocyte depleting induction. Significantly more patients on LET successfully completed 6 months of antiviral prophylaxis (VGCV 31.3% vs. LET 92.1%, p<0.0001). No patients discontinued LET prematurely due to intolerance or breakthrough viral replication. Patients in the VGC cohort were significantly more likely to experience leukopenia (VGCV 95.5% vs. LET 55.3%, p<0.0001) and neutropenia (VGCV 56.7% vs 23.7%, p 0.0012). HCRU was significantly higher in the VGC cohort with 47.8% requiring GCSF (p 0.0063) and 28.4% requiring antiviral dose adjustment (p 0.0001, Table 1) No difference in graft function, post-prophylaxis CMV replication or graft and patient survival were observed through 1-year post-KT (Table 1). The proportion of rejections in the VGCV group was higher than LET, although not statistically significant (VGCV 14.9% vs LET 5.3%, p 0.096).
*Conclusions: In this retrospective real-world cohort study LET for CMV primary prophylaxis is effective and well tolerated. LET prophylaxis is more likely to be completed for the intended duration compared with VGCV prophylaxis; LET is associated with less myelosuppressive toxicity and reduced HCRU. Larger studies are needed to definitively evaluate the impact of LET on rejection rates and transplant outcomes.