Letermovir for treatment of resistant and refractory CMV infections in lung transplant recipients: emergence of resistance

As letermovir comes into clinical use in patients with refractory or resistant disease the development of resistance while on treatment has been observed, suggesting the need for close monitoring during treatment of active infection.

All lung transplant recipients between March 2018 and February 2023, who have been treated with letermovir for ganciclovir-resistant or refractory CMV infection were included in the study and analysed retrospectively.

In total, 58 patients were identified who received rescue therapy with letermovir. Rescue therapy with letermovir was initiated at a median of 10.0 [1.2-87.6] months after LTx and applied for a median of 98 [41- 451] days. In most of the patients (56.1%) monotherapy with letermovir was initiated and no further action was taken. In case of suspicion of treatment failure resistance testing was performed in 19 patients on request of the treating physician. Thereof, 17 tests revealed emergence of letermovir resistance at a median of 74 [41-210] days after treatment start. Negative CMV-CMI, time to decrease of 1 log10 after initiation of letermovir and CMV viral load before rescue therapy were independently associated with a higher risk of development resistance (p=0.001). In 38 of the remaining 40 LTx recipients without letermovir resistance CMV-viral load could be significantly (≥1 log₁₀) decreased after a median of 15.5 [5-31] days upon initiation of letermovir and cleared subsequently after a median of 34 [6-126] days in all of these patients.

In patients with risk factors for the development of resistance a close monitoring during treatment of active infection is recommended.

Publication History

Article published online:
01 March 2024