Letermovir Prophylaxis for Cytomegalovirus Infection in Allogeneic Stem Cell Transplantation: A Real-World Experience

Martino, Massimo; Pitino, Annalisa; Gori, Mercedes; Bruno, Benedetto; Crescimanno, Alessandra; Verde, Federico; Picardi, Alessandra; Tringali, Stefania; Ingrosso, Claudia; Carluccio, Paola; Pastore, Domenico; Musuraca, Gerardo; Paviglianiti, Annalisa; Vacca, Adriana; Serio, Bianca; Storti, Gabriella; Mordini, Nicola; Leotta, Salvatore; Cimminiello, Michele; Prezioso, Lucia; Loteta, Barbara; Ferreri, Anna Maria; Colasante, Fabrizia; Merla, Emanuela; Giaccone, Luisa; Busca, Alessandro; Musso, Maurizio; Scalone, Renato; Renzo, Nicola Di; Marotta, Serena; Mazza, Patrizio; Musto, Pellegrino; Attolico, Immacolata; Selleri, Carmine; Canale, Filippo Antonio; Pugliese, Marta; Tripepi, Giovanni; Porto, Gaetana; Martinelli, Giovanni; Carella, Angelo Michele; Cerchione, Claudio

doi:10.3389/fonc.2021.740079

Cited by 22 publications

(20 citation statements)

References 39 publications

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“…Indeed, with 28.6% of the patients at low risk eventually receiving letermovir in period 2, the low incidence of csCMVi by week 14 (7.9%) was similar to that of the letermovir phase 3 study (7.7%) or real-life studies in which letermovir was used in all patients. 23 , 24 , 25 , 26 The decrease in csCMVi in period 2 compared with that in period 1 was thus explained by the use of letermovir in patients receiving corticosteroids, almost all for aGVHD, which is known to be a major factor in CMV infection. 27 , 28 , 29 , 30 At the same time, we found an important beneficial of letermovir in patients at high risk in csCMVi prevention with an improved and nearly statistically significant OS through 1 year after transplantation.…”

Section: Discussionmentioning

confidence: 99%

The promising efficacy of a risk-based letermovir use strategy in CMV-positive allogeneic hematopoietic cell recipients

et al. 2023

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Letermovir is the first approved drug for cytomegalovirus (CMV) infection prophylaxis in adult CMV-positive patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Since CMV infection risk varies from patient to patient, we evaluated whether a risk-based strategy could be effective. All consecutive CMV-positive adult patients (median age: 56.0 years, IQR: 43.5-64.0) who underwent allo-HCT between 2015 and 2021 (n=316) were included. Letermovir was not used in Period 1 (2015-2017, n=186), whereas during Period 2 (2018-2021, n=130), letermovir was used in high-risk patients but not in low-risk patients, except in those receiving corticosteroids. In high-risk patients, the incidence of clinically significant CMV infection (csCMVi) in Period 2 was lower as compared to Period 1 (p<0.001) by week 14: 10.5% (95% CI 4.6-19.2) vs 51.6% (41.0-61.3) and week 24: 16.9% (8.9-27.0) vs 52.7% (42.0-62.3), respectively. In low-risk patients, although only 28.6% of patients received letermovir in Period 2, csCMVi incidence was also significantly lower (p=0.003) by week 14: 7.9% (2.9-16.3) vs 29.0% (20.2-38.5) and week 24: 11.2% (4.9-20.5) vs 33.3% (23.9-43.0). Among low-risk patients who did not receive letermovir (n=45), 23 (51.1%) patients experienced transient positive CMV DNA without csCMVi by week 14, while it remained negative in 17 (37.8%) patients. In both risk groups, the two periods were comparable for CMV disease, overall survival, progression-free survival, relapse, and non-relapse mortality. We concluded that a risk-based strategy for letermovir use is an effective strategy which maintains the high efficacy of letermovir in high-risk patients but allows some low-risk patients not to use letermovir.

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Section: Discussionmentioning

confidence: 99%

The promising efficacy of a risk-based letermovir use strategy in CMV-positive allogeneic hematopoietic cell recipients

et al. 2023

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“…The efficacy of letermovir prophylaxis in reducing the risk of csCMVi after HSCT is well established. 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 27 However, high rates of late csCMVi have been observed when letermovir prophylaxis is limited to the first 100 days’ posttransplant, especially in high-risk patient groups such as HLA-disparate donor recipients. 11 , 22 A single-center analysis has shown that extending prophylaxis duration beyond 100 days is highly effective in preventing csCMVi in patients with GVHD, another high-risk patient group.…”

Section: Discussionmentioning

confidence: 99%

“… 10 In the pivotal phase 3 trial, letermovir prophylaxis for 14 weeks posttransplant reduced the risk of clinically significant CMV infection (csCMVi), defined as viremia leading to preemptive treatment or CMV end-organ disease, in CMV-seropositive hematopoietic stem cell transplant (HSCT) recipients. 11 Several studies have since corroborated that letermovir continued through day 100 posttransplant is safe and effective CMV prophylaxis in adult donor HSCT 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 or CBT 15 , 21 , 22 recipients. However, a high incidence of delayed-onset csCMVi after letermovir discontinuation has been observed when prophylaxis is limited to the first 14 weeks posttransplant.…”

Section: Introductionmentioning

confidence: 99%

Extended-duration letermovir prophylaxis for cytomegalovirus infection after cord blood transplantation in adults

et al. 2022

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Cord blood transplantation (CBT) can be complicated by a high incidence of clinically significant cytomegalovirus infection (csCMVi). We have investigated the efficacy of extended letermovir prophylaxis in seropositive adult CBT recipients. The aim was to continue prophylaxis for > 6 months (insurance permitting). By day 100, the incidence of csCMVi was 0% in 28 patients who received prophylaxis. Moreover, of 24 patients alive at day 100, none had csCMVi by day 180, having continued prophylaxis for all (n = 20) or part (n = 4) of that period. Overall, 20 patients stopped letermovir at a median of 354 days (range 119-455) post-transplant, with only 5 requiring one (n = 4) or two (n = 1) valganciclovir courses (median total duration 58 days, range 12-67) for post-prophylaxis viremia, with no subsequent csCMVi. There were no attributable letermovir toxicities. Of 62 historic controls who received acyclovir only, 51 developed csCMVi (median onset 34 days, range 5-74) for a day 100 incidence of 82% (95%CI:73-92). Seven patients developed proven/ probable CMV disease and 6 died before day 100 (3 with proven/probable CMV pneumonia). Forty-five patients required extended therapy during the first 6 months for one (n = 10), two (n = 14), or three/persistent (n = 21) csCMVi with 43/51 (84%) developing significant treatment toxicities. Letermovir is highly effective, well tolerated prophylaxis that mitigates CMV infection, CMV-related mortality and antiviral therapy toxicities in CBT recipients. Our data supports prophylaxis duration of at least 6 months after CBT.

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“…Those patients received letermovir (LTM; 480 mg tablet once daily between day 0 and day +28 after allo-HCT and continued until day +100 if no adverse events occurred during the observation period). If LTM was co-administered with cyclosporine, the LTM dosage was decreased to 240 mg once daily [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

A Successful Bridge Therapy Combining Hypomethylating Agents with Venetoclax for Adult Patients with Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia

Bang

Park

Kwag

et al. 2023

Cancers

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Recently, the combination of VEN-HMA has been shown to achieve durable responses in patients with both newly diagnosed (ND) and R/R-AML. We retrospectively evaluated the post-allo-HCT outcomes of 50 patients who received VEN-HMA therapy. In total, 10 were ND and 40 were R/R and, at the time of HCT, the median age was 53 years. In the ND- and R/R-AML groups, the percentage of patients who achieved CR/CRi or MLFS was 90% and 92.5%, respectively. In all, after a median follow-up of 13.7 months, the probabilities of overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) at 1 year were 63.7%, 59.3%, 28.5%, and 12.2%, respectively. In addition, the cumulative incidences of grade II–IV acute graft-versus-host disease (GVHD) and moderate–severe chronic GVHD at 1 year were 28.4% and 37.4%, respectively. In multivariate analysis, the factors associated with a statistically significant impact on OS were VEN-HMA cycle (p = 0.021), ELN risk group (p = 0.041), and the response to VEN-HMA therapy before allo-HCT (p = 0.003). Although 80% of our patients had R/R-AML and 30% underwent a second allo-HCT, our data still suggest that allo-HCT following VEN-HMA therapy is a safe and effective treatment option.

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Letermovir Prophylaxis for Cytomegalovirus Infection in Allogeneic Stem Cell Transplantation: A Real-World Experience

Cited by 22 publications

References 39 publications

The promising efficacy of a risk-based letermovir use strategy in CMV-positive allogeneic hematopoietic cell recipients

The promising efficacy of a risk-based letermovir use strategy in CMV-positive allogeneic hematopoietic cell recipients

Extended-duration letermovir prophylaxis for cytomegalovirus infection after cord blood transplantation in adults

A Successful Bridge Therapy Combining Hypomethylating Agents with Venetoclax for Adult Patients with Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia

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