Prevymis (letermovir) / Merck (MSD), AiCuris - LARVOL DELTA

Use of Letermovir as Secondary Prophylaxis in Cytomegalovirus Resistant Pediatric Heart Transplant Recipients. (PubMed, Clin Transplant) - "In our experience, letermovir was well tolerated and effective in the management of resistant CMV in pediatric heart transplant recipients."

Journal • Cytomegalovirus Infection • Infectious Disease • Pediatrics • Transplantation

Bioequivalent Letermovir Usage for Prophylaxis in Haploidentical Stem Cell Transplantation at High Risk of CMV Reactivation: A Report of Two Cases From India. (PubMed, Cureus) - "While outcomes were favorable, the small sample size and single-center experience represent limitations. Nonetheless, the findings highlight the potential benefit of extended prophylaxis beyond Day 100 and the need for individualized CMV prevention strategies in immunosuppressed populations."

Journal • Bone Marrow Transplantation • Classical Hodgkin Lymphoma • Cytomegalovirus Infection • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Infectious Disease • Lymphoma • Oncology • Primary Immunodeficiency • Transplantation

Abdominal Pain in an Immunocompromised Lung Transplant Recipient Leading to Pneumaturia (ATS 2025) - "His immunosuppressive regimen consisted of mycophenolic acid, prednisone, and tacrolimus, along with prophylactic acyclovir/letermovir, bactrim, and itraconazole...He was empirically treated with piperacillin and tazobactam, which was transitioned to amoxicillin/clavulanate on discharge...Broad spectrum antibiotics alone are often insufficient. Our patient recognized pneumaturia quickly, leading to a timely intervention with a good outcome."

Clinical • Gastrointestinal Disorder • Hematological Disorders • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Leukopenia • Pain • Pulmonary Disease • Respiratory Diseases • Septic Shock • Transplantation • Urology

OFF-LABEL USE OF LETERMOVIR FOR TREATMENT OF CYTOMEGALOVIRUS IN PAEDIATRIC PATIENTS REGARDLESS OF HSCT (ESPID 2025) - "Letermovir was used as monotherapy in one patient and in combination with other CMV-directed treatment including Ganciclovir (n=1) or CMV specific intravenous immunoglobulin (n=2) in the remaining three patients. Three patients received HSCT at a later time point with continuation (n=2) or readministration (n=1) of letermovir (data not included). Conclusions/Learning Points Letermovir may be useful for CMV directed therapy in immunocompromised paediatric patients."

Clinical • Cytomegalovirus Infection • Infectious Disease

USE OF LETERMOVIR AS CYTOMEGALOVIRUS INFECTION PROPHYLAXIS IN GENE THERAPY FOR WISKOTT-ALDRICH SYNDROME: PRELIMINARY SINGLE-CENTER EXPERIENCE (ESPID 2025) - "Both patients had experienced CMV infection but obtained viral load negativization before GT; one of them also required therapy with valganciclovir. At observed timepoints, GT engraftment and outcome did not differ from other patients. We therefore confirmed that letermovir is effective and safe in lentiviral GT; furthermore, our data suggest that it doesn't affect in vivo GT engraftment nor disease correction."

Clinical • Gene therapy • Cytomegalovirus Infection • Human Immunodeficiency Virus • Infectious Disease

Cytomegalovirus Monitoring After Unrelated Hematopoietic Stem Cell Transplantation in North Macedonia – First Results (EFI 2025) - "They were treated with valganciclovir 2 × 450 mg until clearance of the virus was achieved. In our country, patients don't receive pre-emptive therapy with letermovir for CMV management. That is the reason why it is important to have strategy for CMV DNAemia monitoring at least once a week in the first 100 days after HSCT."

Bone Marrow Transplantation • Cytomegalovirus Infection • Hematological Disorders • Infectious Disease • Transplantation • CD33 • CD34

Benefits of primary prophylaxis with letermovir in patients after allogeneic hematopoietic stem cell transplantation for hematologic malignancies. (PubMed, Expert Rev Hematol) - "No risk factors for post-transplant CMV reactivation were identified in LMV group, whereas unrelated donor, donor-negative/recipient-positive CMV-serostatus, and presence of severe aGVHD were associated with higher risk of CMV reactivation in LMV-free control. LMV as CMV primary prophylaxis has a beneficial effect on post HSCT outcome decreasing the incidence of severe aGVHD and cs-CMV reactivation."

Journal • Acute Graft versus Host Disease • Bone Marrow Transplantation • Cytomegalovirus Infection • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Oncology • Transplantation

Role of Donor Cytomegalovirus Serostatus in CMV-Seronegative Recipients of Unrelated Donor Hematopoietic Cell Transplantation with PTCy prophylaxis. (PubMed, Transplant Cell Ther) - "In CMV-seronegative adult AML patients undergoing unrelated donor HCT with PTCy, CMV-seropositive donors are associated with worse OS than CMV-seronegative donors, likely linked to higher relapse risk. These findings underscore the importance of considering donor CMV serostatus in donor selection for CMV-seronegative recipients undergoing HCT with PTCy. Further investigation is necessary to optimize donor selection strategies and improve outcomes in this patient population."

Journal • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Chronic Graft versus Host Disease • Cytomegalovirus Infection • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation

Physiologically based pharmacokinetic modeling supports investigation of potential drug-drug interactions in the pre- and early post-hematopoietic stem cell transplantation stages. (PubMed, Front Pharmacol) - "PBPK models were developed and evaluated for 13 drugs commonly used in HSCT, including cyclosporine, tacrolimus, sirolimus, busulfan, phenytoin, voriconazole, posaconazole, itraconazole, fluconazole, letermovir, fosaprepitant, aprepitant, and omeprazole. This PBPK modeling platform provides a robust tool for identifying and mitigating DDIs in the pre- and early post-HSCT phases. By enabling the optimization of treatment regimens, this model serves as a valuable tool for improving drug safety and therapeutic outcomes for patients with HSCT."

Journal • PK/PD data • Bone Marrow Transplantation • Transplantation

LAVR-289, an Acyclo-Nucleoside Phosphonate, Has Broad-Spectrum Activity against Herpesviruses. (PubMed, ACS Infect Dis) - "Previously, antivirals have been developed against a variety of herpesviruses; these include acyclovir for herpes simplex viruses (HSV1 and 2) and ganciclovir and letermovir for human cytomegalovirus (hCMV). LAVR-289 displays nanomolar efficacy in vitro, is active on viral strains resistant to gold-standard antivirals and is efficacious ex vivo on reconstituted human skin infected with HSV1. In addition, the activity of LAVR-289 against poxviruses and adenoviruses is an indication of its potential for the management of opportunistic virus infections in immunocompromised patients."

Journal • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Herpes Simplex • Infectious Disease

The Importance of Drug Exposure in the Development of Cytomegalovirus Resistance. (PubMed, Int J Antimicrob Agents) - "This disease is routinely managed by antiviral agents including (val)ganciclovir, foscarnet, cidofovir, letermovir, and maribavir. With solid knowledge of these relationships, more predictive in vitro and in vivo markers of clinical efficacy can be identified. Additionally, pharmacokinetic-pharmacodynamic models and combination therapies should be further explored in to improve the management of CMV."

Journal • Review • Cytomegalovirus Infection • Transplantation

CMV Viremia and Colitis in Simultaneous Pancreas-Kidney Transplantation. (PubMed, Am J Case Rep) - "CONCLUSIONS In transplant patients, cytomegalovirus (CMV) infection, particularly when complicated by antiviral resistance, presents significant therapeutic challenges. A strategic approach, including the switch from ganciclovir to maribavir, foscarnet, and finally to letermovir, was critical in successfully managing the infection and preventing severe complications."

Journal • Cytomegalovirus Infection • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Transplantation

REAL-WORLD EFFICACY AND SAFETY OF LETERMOVIR PROPHYLAXIS IN ADOLESCENT PATIENTS UNDERGOING ALLOGENIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: A SINGLE CENTER OBSERVATIONAL STUDY (EHA 2025) - "Aims: To compare the efficacy and safety of letermovir and ganciclovir for cytomegalovirus (CMV) prophylaxis in adolescent patients (aged 14-17 years) undergoing allogenic hematopoietic stem cell transplantation (HSCT). In this single-center real-world study, letermovir exhibited a favourable efficacy and safety profile for CMV prophylaxis in adolescent patients undergoing HSCT. However, further prospective multi-center studies are warranted to validate our conclusion in adolescent patients."

Clinical • Observational data • Real-world • Real-world effectiveness • Real-world evidence • Acute Graft versus Host Disease • Bone Marrow Transplantation • Cytomegalovirus Infection • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Leukopenia • Transplantation

Successful Use of Maribavir for Secondary CMV Prophylaxis in a Pediatric HSCT Patient (ASPHO 2025) - "Despite Letermovir prophylaxis, she developed CMV viremia post-HSCT, leading to primary engraftment failure. She received Foscarnet and Ganciclovir before transitioning to maribavir as secondary prophylaxis during her second HSCT... This case represents the first reported use of maribavir as secondary CMV prophylaxis in a pediatric HSCT patient, demonstrating its safety and efficacy in managing CMV viremia without compromising engraftment or exacerbating comorbidities. Further research is warranted to explore maribavir's role in earlier-stage CMV management and pediatric populations."

Clinical • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Cytomegalovirus Infection • Hematological Disorders • Infectious Disease • Otorhinolaryngology • Pediatrics • Respiratory Diseases • Sinusitis • Transplant Rejection

THIOTEPA-BUSULFAN-FLUDARABINE CONDITIONING REGIMEN WITH ATG/PTCY-BASED GVHD PROPHYLAXIS AS PROMISING APPROACH FOR HAPLOIDENTICAL STEM CELL TRANSPLANTATION IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIA: A SINGLE-CENTER, OPEN-LABEL, PROSPECTIVE STUDY (EHA 2025) - "GVHD prophylaxis included ATG (6 mg/kg) plus low-dose PTCy (50 mg/kg) combined with cyclosporine mycophenolate mofetil and a short course of methotrexate...All patients received letermovir for CMV prophylaxis. Four patients had CMV reactivation and 11 had EBV reactivation all of which resolved with ganciclovir foscarnet or rituximab... These data suggest that the TBF+ATG/PTCy regimen is feasible for haplo-HSCT in ALL with manageable transplant-related toxicity. We will further evaluate the regimen by expanding the patient cohort and extending follow-up which are essential for efficacy and safety analysis."

Clinical • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Dermatology • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lymphoma • Mucositis • Oncology • Pneumonia • Respiratory Diseases • T Acute Lymphoblastic Leukemia • Transplantation

De-novo Initiation of Letermovir vs Valganciclovir for Cytomegalovirus Prophylaxis in AA Kidney Transplant Recipients (clinicaltrials.gov) - P3 | N=60 | Recruiting | Sponsor: Virginia Commonwealth University | Phase classification: P4 ➔ P3

Phase classification • Cytomegalovirus Infection • Transplantation • CYP3A5

SUBSTANTIAL REDUCTION IN CHRONIC GRAFT-VERSUS-HOST DISEASE AND ADEQUATE IMMUNE RECONSTITUTION WITH POST-TRANSPLANT CYCLOPHOSPHAMIDE IN UNRELATED DONOR TRANSPLANTATION: A COMPARATIVE CASE-CONTROL STUDY (EHA 2025) - "Study group included 61 consecutive patients who underwent MUD-HCT between 01/2021 and 09/2024 for myeloid malignancies with PTCy (50mg/kg on days +3 and +4) in addition to tacrolimus/mycophenolate mofetil (MMF) as GvHD prophylaxis. Conditioning regimen was busulfan/fludarabine/thiotepa...There was no difference in the CIN of CMV viremia between the PTCy and the control group for patients who received letermovir prophylaxis (20.6% vs. 24.0%, respectively, p=0.73)... We implemented PTCy for GvHD prophylaxis in the context of MUD-HCT and compared its efficacy to conventional non-PTCy-based strategies. The use of PTCy was not linked to delayed immune reconstitution or increased risk of viral reactivation. Moreover, PTCy was associated with substantial reduction in the occurrence of chronic GvHD, which translated to improved GRFS."

Clinical • Post-transplantation • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Oncology • Transplantation • CD4

LONG TERM OUTCOME OF αßTCR/CD19 DEPLETED HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ADULTS WITH ACUTE LEUKEMIA. A SINGLE CENTER EXPERIENCE. (EHA 2025) - "Conditioning regimen consisted in Treosulfan 30gr/m2 (TREO30) increased to 36 gr/m2 (TREO36) since 2017, associated to Thiotepa 10 mg/Kg and Fludarabine 150 mg/m2...No CMV reactivations or diseases were noted in post letermovir era, while before letermovir CMV reactivation occurred in 30% of analyzed population... These data represent the longest reported follow up of αβTCR/CD19-based depletion haploidentical HSCT in a cohort of adult acute leukemia. This study confirms that this platform is an effective option to achieve deep disease complete remission and improvement in term of overall survival and disease free survival in patients who lack a matched donor or need urgently an allograft, especially if in CR at time of transplant. Moreover the toxicity profile is very tolerable in heavily pretreated population even with higher doses of treosulfan in combination with another alkylant drug."

Clinical • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Leukemia • Oncology • Pediatrics • Transplant Rejection • Transplantation

THE IMPACT OF LETERMOVIR PROPHYLAXIS IN MATCHED SIBLING DONOR HEMATOPOIETIC STEM CELL TRANSPLANTATION: SELECTING THE APPROPRIATE POPULATION FOR RATIONAL PROPHYLACTIC THERAPY (EHA 2025) - "In conclusions, for HSCT recipients from matched siblings, CMV prophylaxis strategies should be guided by risk stratification rather than solely relying on CMV serological status, which is valuable to optimize the prevention strategy. Further validation through larger clinical studies is needed."

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Graft versus Host Disease • Immunology • Transplantation

PRE-TRANSPLANT MNGS-GUIDED LETERMOVIR PROPHYLAXIS REDUCES POST-HSCT CMV REACTIVATION: A PROSPECTIVE RISK STRATIFICATION STUDY (EHA 2025) - "Pre-transplant mNGS detection of CMV sequences identifies high-risk patients for breakthrough reactivation despite LET prophylaxis correlating with inferior survival. Risk stratification incorporating mNGS quantification conditioning intensity BMI and CMV history may optimize prophylactic strategies. These findings advocate for mNGS-based algorithms to guide precision CMV prevention in allo-HSCT."

Clinical • Pre-transplantation • Bone Marrow Transplantation • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Hematological Disorders • Hematological Malignancies • Infectious Disease • Oncology • Transplantation

G-CSF IMPROVES TREG SELECTION AND OUTCOMES OF HLA-HAPLOIDENTICAL HEMATOPOIETIC CELL TRANSPLANTATION WITH T CELL ADOPTIVE IMMUNOTHERAPY (EHA 2025) - "Immune reconstitution was good as viral reactivation occurred only in the early phase after transplant and did not cause any deaths (18 patients (58%) required treatment for HHV6 reactivation in the first month; 5 patients (16%) required treatment of CMV disease after Letermovir prophylaxis)... Treg selection from G-CSF stimulated donors allows for higher purity of Treg final product and its use, together with unstimulated donor Tcons, resulted in lower incidence of aGVHD, even in the absence of immunosuppression, maintaining a potent antileukemic effect. Our study supports the use of Stim-Tregs for immune-suppression free HLA-haploidentical HSCT with Treg-Tcon adoptive immunotherapy."

IO biomarker • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Mucositis • Myelodysplastic Syndrome • Oncology • Pneumonia • Respiratory Diseases • Stomatitis • T Acute Lymphoblastic Leukemia • Transplantation • CD34 • FOXP3 • IL2RA • IL7R • ISG20

INCIDENCE AND RISK FACTORS FOR LATE CYTOMEGALOVIRUS (CMV) BLOOD INFECTIONS AFTER ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT (ALLOHCT) (EHA 2025) - "57% of patients received post-transplant cyclophosphamide (PTCY) for GVHD prophylaxis and 43% received letermovir at any time during their alloHCT...-10.4] 1.9 [0.6-6.4] GVHD Prophylaxis Cyclophosphamide containing 1 1 Methotrexate containing 3.1 [1.5-6.5] 1.4 [0.6-3.5] Other 7.9 [ .8- .0] 4... Multiple risk factors affect the incidence of CMV infection after day+90 of alloHCT. Some increase risk throughout the alloHCT process while others have time-limited effects. Consideration of these risk factors relative to the patient's alloHCT course can potentially predict the risk of CMV infection."

Clinical • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Cytomegalovirus Infection • Graft versus Host Disease • Immunology • Infectious Disease • Transplantation

LONG TERM FOLLOW UP OF THE BATMO PROTOCOL (BEST-ANTIMICROBIAL-THERAPY-TMO) AND COMPARISON WITH HYSTORICAL DATA (EHA 2025) - "The main features of this protocol are the lack of fluoroquinolones prophylaxis during neutropenic phase of allo-SCT the administration of posaconazole in high-risk patients (pts) and of letermovir in CMV-positive pts from day 0 to day +100. Sistematic use of posaconazole as fungal prophylaxis is effective in maintaining a low incidence of proven/possible IFD despite the increase of risk factors (e.g. more Haplo donors in Cohort B). Data on the antimicrobial susceptibility of BSI isolates MDR-colonizing bacteria and the use of new antimicrobials are currently under investigation."

Clinical • Acute Graft versus Host Disease • Febrile Neutropenia • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Neutropenia • Pneumonia • Respiratory Diseases

Epstein-Barr virus infection following allogeneic hematopoietic stem cell transplantation in the era of letermovir for cytomegalovirus prophylaxis. (PubMed, Exp Hematol Oncol) - "Our findings emphasized that although letermovir prophylaxis did not increase the risk of EBV DNAemia in allo-HCT recipients, it was associated with a higher incidence of PTLD. Further studies focusing on immune reconstitutiom dynamics are warranted to elucidate the underlying pathophysiology of EBV-PTLD under letermovir pressure."

Journal • Bone Marrow Transplantation • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Infectious Disease • Transplantation • CD8

ELISPOT as a predictor of clinically significant cytomegalovirus infection after hematopoietic cell transplantation in letermovir recipients. (PubMed, Bone Marrow Transplant) - "Clinical risk factors (e.g., early CMV infection, acute graft-versus-host disease) predicted late csCMV and improved the predictive value of CMV-CMI testing. Thus, standardized CMV-CMI, after HCT, combined with clinical factors can be used to accurately stratify the risk of late csCMV infection after letermovir prophylaxis."

Journal • Acute Graft versus Host Disease • Cytomegalovirus Infection • Graft versus Host Disease • Immunology • Infectious Disease • Transplantation