Abstract
Cytomegalovirus (CMV) prophylaxis with valganciclovir is the standard of practice in most transplant centers, but treatment-related leukopenia can limit valganciclovir’s use. Therefore, we evaluated letermovir, a novel antiviral agent recently approved for use in hematopoietic cell transplant patients as CMV prophylaxis, in lung transplant recipients unable to tolerate valganciclovir due to severe leukopenia. We performed a retrospective analysis of all lung transplant patients at our center who received letermovir for CMV prophylaxis between 1 December 2018 and 1 January 2020. A repeated measures mixed model was used to analyze white blood cell (WBC) trends, and descriptive statistics were used to analyze secondary endpoints, including CMV DNAemia, renal function, immunosuppression dosing, and allograft function. Seventeen patients were administered letermovir during the study period due to valganciclovir-induced leukopenia (median WBC nadir 1.1 K/uL, range <0.30–2.19 K/uL). Median WBC improvement was noted in 15 (88.2%) patients after starting letermovir. Breakthrough CMV DNAemia necessitating treatment occurred in two patients, with one of the two cases being due to patient noncompliance. CMV resistance to letermovir was detected in two patients, necessitating a change to an alternative agent in one of these patients. No major side effects were reported in any patient. Letermovir is a generally safe and effective alternative for CMV prophylaxis in lung transplant recipients unable to tolerate valganciclovir due to leukopenia.
Highlights
Introduction iationsCytomegalovirus (CMV) infection is an important cause of morbidity and mortality in lung transplantation and is associated with impaired allograft function, development of bronchiolitis obliterans syndrome, and decreased long-term survival [1]
Lung transplant patients are at increased risk of leukopenia from valganciclovir, a risk accentuated by other myelosuppressive agents required for allograft preservation [9]
In an effort to minimize the risk of leukopenia in our patients due to valganciclovir, we utilized letermovir, a novel CMV antiviral, for prophylaxis in patients with valganciclovir-induced leukopenia
Summary
Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality in lung transplantation and is associated with impaired allograft function, development of bronchiolitis obliterans syndrome, and decreased long-term survival [1]. Current guidelines recommend antiviral prophylaxis against CMV for 6–12 months after lung transplant, typically with valganciclovir [2]. Bone marrow suppression and leukopenia are wellknown adverse effects of valganciclovir and, if severe enough, can limit its utility [2]. The incidence of valganciclovir-associated leukopenia has been reported to be as high as 20%. Letermovir, a novel antiviral agent approved for CMV prophylaxis in hematopoietic cell transplantation (HCT) [4], preferentially targets and inhibits the CMV viral terminase, a virus-specific enzyme complex encoded by genes UL51, UL56, and UL89 and Licensee MDPI, Basel, Switzerland.
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