P1324: a risk-based strategy for the use of letermovir in cmv-positive recipients of allogeneic hematopoietic cell transplantation

Background: Letermovir has been approved since 2018 for the prevention of CMV infection and disease in adult CMV-seropositive recipients after allogeneic hematopoietic cell transplant (allo-HCT). It is an orally administered treatment but expensive and a potential source of drug interactions. Its benefit could therefore vary according to the risk of CMV infection, which depends on the transplantation modalities and the characteristics of the donor/recipient couple. Aims: The objective of this study was to evaluate the interest of a letermovir administration strategy based on the risk of CMV infection in allo-HCT recipients. Methods: The study was led according to the Declaration of Helsinki, and patients provided informed consent about the retrospective use of their clinical data. All consecutive CMV-seropositive adult patients who underwent allo-HCT from January 1, 2015, to July 31, 2021 at the University Hospital of Lille, France, were included. Patients were divided into two periods based on the date of transplantation: a first one (P1: 2015-2017) during which letermovir was not administered and a second one (P2: 2018-2021) during which letermovir was administered based on the risk of CMV infection, calculated according to a previously published score (Beauvais et al, BMT 2021). Specifically, during P2 in high-risk patients, letermovir was administered systematically, whereas in low-risk patients, letermovir was administered only in those receiving systemic corticosteroid therapy. Results: Three hundred and sixteen CMV positive patients were included (186 in P1, 130 in P2). The median age was 56 years (IQR: 43.5-64.0) and 52.5% were male. Patient characteristics and transplantation modalities between the 2 periods were comparable. The median follow-up was 60.3 months for P1 and 18.0 months for P2. In high-risk patients, with systematic letermovir use in P2, clinically significant CMV infection decreased substantially compared with P1: 10.5% [IC95: 4.6-19.2] vs 51.6% [41.0-61.3] at 14 weeks, 16.9% [8.9-27.0] vs 52.7% [42.0-62.3] at 24 weeks, and 53.8% [43.0-63.3] vs 28.2% [17.3-40.2] at 1 year post allo-HCT, p < 0.0001. CMV disease was not significantly different between the 2 periods: 0% vs 3.2% [0.9-8.4] at 14 weeks, 1.5% [0.1-7.2] vs 4.3% [1.4-9.9] at 24 weeks, and 3.3% [0.6-10.3] vs 4.3% [1.4-9.9] at 1 year post allo-HCT, p = 0.69. In low-risk patients, only 18/63 (28.6%) patients received letermovir due to the initiation of systemic corticosteroid therapy. The median time to initiation from allo-HCT was 28 days (range: 16-50). Despite this limited use of letermovir, clinically significant CMV infection also decreased substantially: 7.9% [2.9-16.3] vs 29.0% [20.2-38.5] at 14 weeks, 11.2% [4.9-20.5] vs 33.3% [23.9-43.0] at 24 weeks, and 12.9% [6.0-22.6] vs 34.4% [24.9-44.1] at 1 year post allo-HCT, p = 0.0025. A majority of low-risk patients (45/63; 71.4%) did not receive letermovir. Most had blips, all of which resolved spontaneously by week 14. CMV disease was not significantly different between the 2 periods: 0% vs 0% at 14 weeks, 1.7% [0.1-8.0] vs 1.1% [0.1-5.3] at 24 weeks, and 1.7% [0.1-8.0] vs. 2.2% [0.4-6.9] at 1 year post allo-HCT, p = 0.85. For high-risk and low-risk patients, overall survival, progression-free survival, incidence of relapse, and relapse-free mortality were not significantly different between the 2 periods. Image:Summary/Conclusion: A risk-based strategy for the use of letermovir, rather than systematically, is feasible in CMV-positive recipients of allo-HCT without increasing the risk of clinically significant CMV infection and CMV disease.