Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy

Curr Hematol Malig Rep. 2020 Apr;15(2):90-102. doi: 10.1007/s11899-020-00557-6.

Abstract

Purpose of review: CMV DNA polymerase inhibitors such as ganciclovir and foscarnet have dramatically reduced the burden of CMV infection in the HCT recipient. However, their use is often limited by toxicities and resistance. Agents with novel mechanisms and favorable toxicity profiles are critically needed. We review recent developments in CMV antivirals and immune-based approaches to mitigating CMV infection.

Recent findings: Letermovir, an inhibitor of the CMV terminase complex, was approved in 2017 for primary CMV prophylaxis in adult seropositive allogeneic HCT recipients. Maribavir, an inhibitor of the CMV UL97 kinase, is currently in two phase 3 treatment studies. Adoptive immunotherapy using third-party T cells has proven safe and effective in preliminary studies. Vaccine development continues, with several promising candidates currently under study. No longer limited to DNA polymerase inhibitors, the prevention and treatment of CMV infections in the HCT recipient is a rapidly evolving field which should translate into improvements in CMV-related outcomes.

Keywords: Antiviral; Cytomegalovirus; Filociclovir; Hematopoietic cell transplant; Letermovir; Maribavir.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus / pathogenicity
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / therapy*
  • Cytomegalovirus Infections / virology
  • Cytomegalovirus Vaccines / therapeutic use
  • Drug Resistance, Viral
  • Foscarnet / therapeutic use
  • Ganciclovir / therapeutic use
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Immunocompromised Host
  • Immunosuppressive Agents / adverse effects
  • Immunotherapy / adverse effects
  • Immunotherapy / trends*
  • Immunotherapy, Adoptive / trends
  • Molecular Targeted Therapy / adverse effects
  • Molecular Targeted Therapy / trends*
  • Opportunistic Infections / immunology
  • Opportunistic Infections / therapy*
  • Opportunistic Infections / virology
  • Risk Factors
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Cytomegalovirus Vaccines
  • Immunosuppressive Agents
  • Foscarnet
  • Ganciclovir