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Abstract: SA-PO1124

Treatment of Valganciclovir-Resistant Cytomegalovirus with Letermovir

Session Information

Category: Trainee Case Report

  • 1902 Transplantation: Clinical

Authors

  • Raines, Nathan H., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Morales, Alexander, Memorial Hospital of Rhode Island/Alpert Medical School of Brown University, West Warwick, Rhode Island, United States
  • Nissaisorakarn, Pitchaphon, Jacobi Medical Center, Bronx, New York, United States
  • Pandit, Amar, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Aala, Amtul, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
Introduction

Cytomegalovirus (CMV) resistance to ganciclovir is an important concern post- kidney transplant. Resistance is often mediated by one of two mutations: UL97, which encodes a kinase responsible for phosphorylation and activation of ganciclovir; and UL54, which encodes the viral DNA polymerase targeted by ganciclovir (Vez et al, Clin K J 2014). Alternatives to ganciclovir include foscarnet and cidofivir, but their use can be limited by nephrotoxicity and marrow suppression. Letermovir is an anti-CMV agent approved by the FDA for prophylaxis against CMV infection post-transplant. It inhibits CMV replication by binding to the terminase complex not affected by the mutations seen in ganciclovir-resistant CMV, and has minimal myelosuppresive and nephrotoxic effects.

Case Description

This is a 73 year old woman with a history of ESRD due to anti-GBM disease who underwent deceased donor renal transplant in January 2019. She was considered high risk for CMV as a CMV IgG negative patient who received a kidney from a CMV IgG positive donor. In February 2019 she was found to have a detectable CMV viral load, rising throughout March and April despite increased doses of valgancyclovir. She was admitted in April 2019 for treatment with Foscarnet. CMV resistance genotyping showed a UL97 mutation predicting Ganciclovir resistance. CMV viral load peaked at 4.0 log 10 IU/ml and began to downtrend after 1 week of Foscarnet. She then developed AKI and pancytopenia with severe neutropenia which was likely Foscarnet-induced. In consultation with infectious disease we started oral letermovir 480mg twice for 7 days then converted to daily dosing until viral load becomes undetectable. Her viral load has downtrended to < 2.1 log 10 IU/ml on letermovir after 2 weeks of therapy. Neutropenia has recovered, and her AKI has improved.

Discussion

Letermovir is currently being studied for treatment of CMV resistant to ganciclovir (ID NCT03728426, phase 2 investigation). Here we present a case of an individual with proven UL97 mutation-driven ganciclovir-resistant CMV who developed severe side effects precluding further use of foscarnet and was started on Letermovir for treatment of CMV. CMV viral load improved to barely detectable levels on treatment with letermovir alone, without marrowsuppressive or nephrotoxic side effects.