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

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 3months of treatment initiation. Conclusions: Measurement of letermovir concentration and genotyping should be recommended for patient follow-up during letermovir therapy.