Use of letermovir in off-label indications: Infectious Diseases Working Party of European Society of Blood and Marrow Transplantation retrospective study

Styczyński, Jan; Tridello, Gloria; Xhaard, Aliénor; Medinger, Michael; Mielke, Stephan; Taskinen, Mervi; Blijlevens, Nicole M A; Rodríguez, Migdalia; Solano, Carlos; Nikolousis, Emmanouil; Biffi, Alessandra; Groll, Andreas H.; Junghanß, Christian; Tsirigotis, Panagiotis; Lioure, Bruno; Šrámek, Jiří; Holler, Ernst; Galaverna, Federica; Fagioli, Franca; Knelange, Nina; Wendel, Lotus; Gil, Lidia; Cámara, Rafael de la; Mikulska, Małgorzata; Ljungman, Per

doi:10.1038/s41409-020-01166-w

Cited by 36 publications

(33 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regarding CMV, the most common viral threat after HSCT, the use of the new antiviral letermovir holds promises. 40 However, several other viruses, such as ADV, are poorly controlled by pharmacological interventions. For this reason, adoptive infusion of virus-specific or nonspecific donor lymphocytes has been adopted.…”

Section: Discussionmentioning

confidence: 99%

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different nonmalignant disorders

et al. 2022

Self Cite

View full text Add to dashboard Cite

Several non-malignant disorders (NMDs), either inherited or acquired, can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). Between January 2012 and April 2020, 70 consecutive children affected by primary immunodeficiencies, inherited/acquired bone marrow failure syndromes, red blood cell disorders or metabolic diseases, lacking a fully-matched donor or requiring urgent transplantation, underwent TCRαβ/CD19-depleted haploidentical HSCT from an HLA-partially matched relative as part of a prospective study (#NCT01810120). Median age at transplant was 3.5 years (range 0.3-16.1); median time from diagnosis to transplant was 10.5 months (2.7 for SCID patients). Primary engraftment was obtained in 51 patients, while 19 and 2 patients experienced either primary or secondary graft failure (GF), the overall incidence of this complication being 30.4%. Most GFs were observed in children with disease at risk for this complication (e.g., aplastic anemia, thalassemia). All but 5 patients experiencing GF were successfully retransplanted. Six patients died of infectious complications (4 had active/recent infections at time of HSCT), the cumulative incidence of transplant-related mortality (TRM) being 8.5%. Cumulative incidence of grade I-II acute GvHD was 14.4% (no patient developed grade III-IV acute GVHD). Only one patient at risk developed mild chronic GvHD. With a median follow-up of 3.5 years, the 5-year probability of overall and disease-free survival was 91.4% and 86.8%, respectively. In conclusion, TCRαβ/CD19-depleted haploidentical HSCT from an HLA-partially matched relative is confirmed to be an effective treatment for children with NMDs. Prompt donor availability, low incidence of GvHD and TRM make this strategy an attractive option in NMDs patients.

show abstract

Section: Discussionmentioning

confidence: 99%

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different nonmalignant disorders

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…LMV is a drug that breaks the paradigm of anti-CMV management by shifting preventive therapy to prophylaxis. Additionally, recent studies have indicated needs for prophylaxis in children [31] and secondary prophylaxis [32].…”

Section: Discussionmentioning

confidence: 99%

Real-world experience with letermovir in primary prophylaxis of cytomegalovirus in adult patients after hematopoietic cell transplantation: summary of reported data

Czyżewski

Styczyński

2021

Acta Haematol Pol.

Self Cite

View full text Add to dashboard Cite

Introduction: Letermovir (LMV) is a new antiviral agent approved in 2017 for prophylaxis to prevent cytomegalovirus (CMV) reactivation in CMV-seropositive allogeneic hematopoietic cell transplant recipients. Numerous reports on real--world experiences with LMV have been presented at international hematology and hematopoietic cell transplantation meetings. The objective of this study was to summarize data reported 2019-2020 on primary prophylaxis with LMV in adult patients. Methods:We analyzed 19 studies published or presented in 2019 and 2020, including two studies presented twice.Results: An overall 817 patients received primary prophylaxis with LMV. In 12 studies with a control group, the rate of breakthrough infection was 99/577 (17.2%) vs. 874/1,525 (57.3%), odds ratio (OR) =6.5 [95% confidence interval (CI) =5.1-8.2), p <0.0001]. In seven studies without a control group, the rate was 17/240 (7.1%). Overall breakthrough infection occurred in 116/817 (14.2%) patients on LMV primary prophylaxis vs. 874/1,525 (57.3%) without prophylaxis, OR =8.1 (95% CI =6.5-10.1), p <0.0001.Conclusions: LMV when used for primary prophylaxis challenges the standard of care for CMV reactivation based on preemptive therapy. Presented real-world data shows a significant improvement in reducing the risk of any CMV viremia and clinically significant CMV infection in all reported studies performed so far. LMV is a drug that breaks the paradigm of preventive therapy by moving it from pre-emptive treatment to prophylaxis.

show abstract

“…Letermovir has recently been available in clinical practice according to a previous phase 3 trial. 25,26 After approval of letermovir, several real-world experiences have been reported on its use in primary 46,47 and secondary prophylaxis, 48,49 and they have demonstrated a significant reduction in CMV reactivation. Recently, Johnsrud et al reported a single-center experience in which 114 patients received letermovir prophylaxis.…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus gastroenteritis in patients with acute graft-versus-host disease

et al. 2022

View full text Add to dashboard Cite

A pre-emptive strategy has successfully decreased cytomegalovirus (CMV) disease after allogeneic hematopoietic cell transplantation (HCT). However, some recipients still develop CMV gastroenteritis, especially after acute graft-versus-host disease (aGVHD), and its incidence, risk factors, and prognostic impact remain to be elucidated. We retrospectively analyzed 3759 consecutive adult patients who developed grade II-IV aGVHD using a Japanese registry database. The cumulative incidence of CMV gastroenteritis was 5.7% by day 365 from the development of grade II-IV aGVHD. Advanced age (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.16-2.22; P = 0.004), GVHD prophylaxis with mycophenolate mofetil and calcineurin inhibitor (HR, 1.73; 95% CI, 1.08-2.77; P = 0.024), lower-gut aGVHD (HR, 2.17; 95% CI, 1.58-2.98; P < 0.001), and the use of systemic steroids (HR, 1.78; 95% CI, 1.16-2.74; P = 0.008) were independent risk factors for CMV gastroenteritis. Development of CMV gastroenteritis was associated with an increased risk of nonrelapse mortality (HR, 1.89; 95% CI, 1.50-2.39; P < 0.001). Moreover, letermovir prophylaxis significantly reduced both the incidence of CMV gastroenteritis (HR, 0.50; 95% CI, 0.25-0.99; P = 0.047) and the risk of nonrelapse mortality (HR, 0.72; 95% CI, 0.52-0.99; P = 0.043). In summary, CMV gastroenteritis is a life-threatening complication that sets the need for preventive strategies with letermovir and targeted surveillance.

show abstract

Use of letermovir in off-label indications: Infectious Diseases Working Party of European Society of Blood and Marrow Transplantation retrospective study

Cited by 36 publications

References 20 publications

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different nonmalignant disorders

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different nonmalignant disorders

Real-world experience with letermovir in primary prophylaxis of cytomegalovirus in adult patients after hematopoietic cell transplantation: summary of reported data

Cytomegalovirus gastroenteritis in patients with acute graft-versus-host disease

Contact Info

Product

Resources

About