Letermovir breakthroughs during the French Named Patient Programme: interest of monitoring blood concentration in clinical practice

S Alain; L Feghoul; S Girault; Q Lepiller; E Frobert; D Michonneau; A Berceanu; S Ducastelle-Lepretre; V Tilloy; E Guerin; J Le Goff; G Peytavin; S Hantz

doi:10.1093/jac/dkaa135

Letermovir breakthroughs during the French Named Patient Programme: interest of monitoring blood concentration in clinical practice

J Antimicrob Chemother. 2020 Aug 1;75(8):2253-2257. doi: 10.1093/jac/dkaa135.

Authors

S Alain^{1

2

3}, L Feghoul⁴, S Girault⁵, Q Lepiller⁶, E Frobert⁷, D Michonneau⁸, A Berceanu⁹, S Ducastelle-Lepretre¹⁰, V Tilloy^{2

3}, E Guerin³, J Le Goff⁴, G Peytavin¹¹, S Hantz^{1

2}

Affiliations

¹ UMR Inserm 1092, RESINFIT, Université de Limoges, Limoges, France.
² National Reference Centre for Herpesviruses, Bacteriology Virology Hygiene Department, CHU Limoges, Limoges, France.
³ Medical Genomic and Bioinformatics Units, GenoLim, CHU Limoges, Limoges, France.
⁴ Virology Department, Hôpital Saint Louis, Université de Paris, Paris, France.
⁵ Haematology Department, CHU Limoges, Limoges, France.
⁶ Virology Department, CHU Besançon, Besançon, France.
⁷ Virology Department, CBPE, Hospices Civils de Lyon, Lyon, France.
⁸ Haematology and Transplantation Unit, Hôpital Saint Louis, Université de Paris, Paris, France.
⁹ Haematology and Transplantation Unit, CHU Besançon, Besançon, France.
¹⁰ Haematology and Transplantation Unit, Hôpital E Herriot, Lyon, France.
¹¹ APHP, Pharmacology & Toxicology Laboratory and IAME, Inserm UMR 1137, Université Paris 7, Paris, France.

PMID: 32413116
DOI: 10.1093/jac/dkaa135

Abstract

Objectives: To analyse mechanisms of letermovir breakthrough during compassionate primary and secondary prophylaxis.

Methods: Mechanisms of letermovir breakthrough during compassionate primary and secondary prophylaxis were analysed in four patients from the French Named Patient Programme by the French National Reference Centre for Herpesviruses.

Results: Of three absolute resistance cases, two were associated with treatment interruption or low letermovir concentrations in blood. A fourth case of breakthrough was not associated with resistance. Next-generation sequencing (NGS) genotyping confirmed rapid emergence of resistant mutants, within 3 months of treatment initiation.

Conclusions: Measurement of letermovir concentration and genotyping should be recommended for patient follow-up during letermovir therapy.

© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetates / therapeutic use
Antiviral Agents / therapeutic use
Cytomegalovirus Infections* / drug therapy
Cytomegalovirus*
Humans
Quinazolines

Substances

Acetates
Antiviral Agents
Quinazolines
letermovir