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Abstract: TH-PO995

Viral Resistance and Neutropenia/Leukopenia with Letermovir (LET) vs. Valganciclovir (VGCV) as Cytomegalovirus (CMV) Prophylaxis in Adult Kidney Transplant Recipients (KTRs): A Phase 3 Randomized Study

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Vincenti, Flavio, University of California at San Francisco, San Francisco, California, United States
  • Limaye, Ajit, University of Washington Medical Center, Seattle, Washington, United States
  • Budde, Klemens, Charité-Universitätsmedizin Berlin, Berlin, Germany
  • Humar, Atul, University Health Network, Toronto, Ontario, Canada
  • Garcia-Diaz, Julia, Ochsner Medical Center, New Orleans, Louisiana, United States
  • Carroll, Robert Peter, Central Northern Adelaide Renal and Transplantation Service, Adelaide, South Australia, Australia
  • Florescu, Diana F., University of Nebraska Medical Center, Omaha, Nebraska, United States
  • Murata, Yoshihiko, Formerly Merck & Co., Inc., Rahway, New Jersey, United States
  • Strizki, Julie, Merck & Co., Inc., Rahway, New Jersey, United States
  • Teal, Valerie, Merck & Co., Inc., Rahway, New Jersey, United States
  • Gilbert, Christopher L., Merck & Co., Inc., Rahway, New Jersey, United States
  • Haber, Barbara A., Merck & Co., Inc., Rahway, New Jersey, United States
Background

VGCV is indicated for CMV prophylaxis in adult donor CMV-seropositive/recipient CMV-seronegative (D+/R-) KTRs; use is limited by myelosuppression and need to adjust dose for renal function, placing KTRs at risk for CMV breakthrough/resistance. LET is non-myelotoxic and needs no renal adjustment; it is approved for CMV prophylaxis in adult R+ allogeneic hematopoietic cell transplant recipients. This Phase 3, double-blind, non-inferiority study (NCT03443869) evaluated CMV prophylaxis with LET vs VGCV in adult D+/R- KTRs.

Methods

KTRs were randomized (1:1) ≤7 days post-KT to receive LET 480 mg PO QD with acyclovir (400 mg PO BID) or VGCV (900 mg PO QD) through Week 28 and followed through Week 52 post-KT. The primary endpoint was proportion of participants (pts) with adjudicated CMV disease through Week 52 post-KT. Genotyping for resistance-associated variants (RAVs) was performed when pts were evaluated for CMV disease or when study medication was discontinued due to CMV viremia.

Results

The proportion of pts with CMV disease through Week 52 post-KT was 10.4% with LET (N=289) vs 11.8% with VGCV (N=297). The rate of CMV viremia through Week 28 post-KT was 2.1% with LET vs 8.8% with VGCV. No LET RAVs (pUL51/pUL56/pUL89) were found among 52 evaluated LET pts; VGCV RAVs were found in 8/66 (12.1%) evaluated VGCV pts (pUL54, n=2; pUL97, n=7). The incidence of neutropenia/leukopenia was lower with LET vs VGCV (overall, 26.0% vs 64.0% [p<0.0001]; Grade 3/4 neutropenia, 2.1% vs 7.9%; Grade 3/4 leukopenia, 2.7% vs 6.6%). Rates of treatment discontinuation due to adverse events (AEs) were 4.1% for LET vs 13.5% for VGCV (most commonly due to neutropenia/leukopenia).

Conclusion

In preventing CMV disease in D+/R- KTRs through Week 52 post-KT, LET was non-inferior to VGCV. Neutropenia/leukopenia were the most common AEs leading to discontinuation of CMV prophylaxis. The prevalence of viral RAVs was lower in LET (0%) vs VGCV (12.1%) pts.

Funding

  • Commercial Support