- |||||||||| Orencia (abatacept) / BMS
Abatacept and Post Transplant Cyclophosphamide Based Regimen for Graft Versus Host Disease Prevention in High-Risk Stem Cell Transplantation from Unrelated Donor Is Safe and Feasible, with Low Non- Relapse Mortality (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3253;
Introduction The combination of Abatacept (ABA) with tacrolimus and methotrexate is FDA-approved for the prevention of acute graft versus host disease in patients undergoing allogeneic hematopoietic stem cell transplantation (HCT) from matched unrelated donors (MUD) or one allele mismatched unrelated donors (MMUD)...Conditioning regimens were Busulfan based (Flu-Bu) in12 patients, Melphalan based (Flu-Mel) in 9 patients and Fludarabine/Cyclophosphamide/Total Body Irradiation in 4 patients...Patients received institutional antimicrobial prophylaxis with Acyclovir, Levofloxacin, Posaconazole, letermovir and Bactrim...However, there was a gradual recovery of T and B cell by day 100. This is a single institution, limited patient cohort, and prospective studies are undergoing to further evaluate and optimize the proposed regimen for GVHD prevention in MUD/MMUD recipients.
- |||||||||| Prevymis (letermovir) / Merck (MSD)
CMV Specific T Cell Polyfunctionality after HCT: A Detailed Analysis of the Impact of Steroid Exposure, Immunosuppressive Regimens and Viral Reactivation (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3204;
Here we comprehensively assessed the impact of GC exposure (dose, timing), mycophenolate mofetil (MMF), posttransplant cyclophosphamide (PTCy), and CMV reactivation on CMV T-cell responses after HCT...Prednisone-equivalent doses were categorized as follows : low (>0 - <0.5 mg/kg) intermediate (?0.5-<1 mg/kg), or high (?1 mg/kg)...Antiviral prophylaxis for CMV was used in all recipients of cord blood grafts (high-dose valacyclovir) and those transplanted after 2018 (letermovir, 21%); all patients underwent weekly CMV PCR monitoring...However, intermediate or high doses of GC, especially when given within 2-4 weeks before testing, and concomitant treatment with MMF had significant inhibitory effect on both CD4 and CD8 polyfunctional CMV-specific responses. These data will be critical to design effective T-cell therapy trials.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
Long-Term Follow up of a Prospective Pilot Study of an ?/? T-Lymphocyte Depleted Graft Conditioned with a Reduced Intensity Regimen in Patients with Hematologic Malignancies (Room 6CF (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_1481;
P1
Patients were conditioned with rabbit anti-thymocyte globulin (ATG) 2mg/kg/daily x3, fludarabine 30mg/m2 daily x5 and TBI 2Gy daily x2 and received post-transplant cyclophosphamide (PT-Cy) 50mg/kg/daily x2 with aim to further reduce host T cells to enhance engraftment, and rituximab 200mg/m2 x1 to reduce risk of EBV-driven post-transplant lymphoproliferative disorder (PTLD)...CMV viremia was detected in four patients; all were CMV seropositive recipients who received letermovir prophylaxis...The low incidence of severe acute GVHD and absence of chronic GVHD allowed patients to be treated successfully even at time of disease relapse. Based on the promising outcomes of this pilot study, future research will focus on validating these findings in a larger cohort through a phase II study.
- |||||||||| Review, Journal: Challenges and advances in the management of HCMV infections (Pubmed Central) - Nov 5, 2024
Ganciclovir, foscarnet and cidofovir, which interfere with the activity of the viral polymerase pUL54, are widely used in the treatment of transplant patients...On the other hand, hyperimmune immunoglobulins and valaciclovir have been shown to have a protective effect on the fetus...Letermovir and maribavir have been developed to inhibit new targets, respectively the terminase complex and UL97 protein kinase...Finally, with the development of mRNA vaccines, the hope of one day seeing a prophylactic HCMV vaccine has never been greater. New therapeutic approaches are also being explored, but they still require extensive preclinical and clinical evaluation.
- |||||||||| Cytovene (ganciclovir) / Roche
Journal: Cytomegalovirus chronic retinal necrosis with ganciclovir resistance: a case report. (Pubmed Central) - Oct 8, 2024
Treatment with ganciclovir is effective but frequently leads to resistance, as in our case. In this situation, combination therapy with letermovir and leflunomide, particularly in the setting of rheumatoid arthritis where leflunomide can also have an anti-inflammatory effect, can be considered.
- |||||||||| Prevymis (letermovir) / Merck (MSD), Valcyte (valganciclovir) / Roche, Mitsubishi Tanabe
Journal: Management of Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients (Pubmed Central) - Oct 5, 2024
Secondary prophylaxis with valganciclovir (antiviral drug) is recommended after an episode of active infection, while preemptive and disease treatment is based on monitoring viral load and clinical response. The aim of this guideline is to improve the approach to CMV infection in HSCT patients, ensuring an effective and safe preventive and therapeutic approach.
- |||||||||| Prevymis (letermovir) / Merck (MSD), Livtencity (maribavir) / Takeda, GSK
Review, Journal: Viral infection after hematopoietic stem cell transplantation. (Pubmed Central) - Sep 26, 2024
The detection of letermovir and maribavir resistance mutations highlights an ongoing clinical challenge in the management of CMV. Although improvements in patient management for several important posttransplantation viral infections have been reported, an unmet medical need still exists for other viruses occurring in this high-risk population.
- |||||||||| Prevymis (letermovir) / Merck (MSD), Valcyte (valganciclovir) / Roche, Mitsubishi Tanabe
Enrollment open, Trial completion date, Monotherapy: LUCY-1: Letermovir-based Dual Therapy for Treatment of Cytomegalovirus Infections (clinicaltrials.gov) - Sep 26, 2024
P3, N=80, Recruiting,
Although improvements in patient management for several important posttransplantation viral infections have been reported, an unmet medical need still exists for other viruses occurring in this high-risk population. Not yet recruiting --> Recruiting | Trial completion date: Jul 2027 --> Nov 2027
- |||||||||| Prevymis (letermovir) / Merck (MSD)
Letermovir Prophylaxis for CMV Infection in Allogeneic Stem Cell Transplantation: A Retrospective Single Center Analysis (Exhibition Hall (3F)) - Sep 24, 2024 - Abstract #ICBMT2024ICBMT_333;
Conclusions : Although the results did not reach statistical significance due to the small sample size, in this study, the use of letermovir as CMV prophylaxis in allo-SCT recipients demonstrated a reduction in the incidence of CMV reactivation compared to a control group in high risk patients. Study design The cumulative incidence of CMV reactivation at 100 days (a), and 180 days (b)
- |||||||||| Cytomegalovirus in Hematopoietic Cell Transplantation: Prophylaxis & Treatment (Room D (1F)) - Sep 24, 2024 - Abstract #ICBMT2024ICBMT_178;
In the 1990s, the effectiveness of prophylaxis using traditional antiviral agents including acyclovir or ganciclovir was compared...In addition to traditional antiviral agents (i.e. ganciclovir, foscarnet, and cidofovir), maribavir has been introduced for treatment of refractory or resistant CMV infection...Landscape of CMV prevention and management after HCT is evolving with the introduction of newer antiviral agents. Further studies are needed to investigate letermovir breakthrough cases with CMV resistance testing, ongoing risk factors after stopping prophylaxis, management of recurrent refractory or resistant CMV cases, and immune monitoring strategies.
- |||||||||| Prevymis (letermovir) / Merck (MSD)
Transplants from Unrelated Donors in Europe: Where We Are and Where We Are Going (Room D (1F)) - Sep 24, 2024 - Abstract #ICBMT2024ICBMT_158;
Despite the high and increasing number of volunteer stem cell donors there is an increase in donor cancellation and a considerable delay in donor availability over the last years. The development of Haplo-identical stem cell transplantation by using post- transplant Cyclophosphamide and the much faster availability of an haplo-identical donor has led to an increase of haplo-identical donor cell transplantation and current ongoing studies address the question whether haplo-identical donor should be preferred to MUD.
- |||||||||| Prevymis (letermovir) / Merck (MSD)
CMV Prophylaxis with Letermovir in Allo HSCT - Extended Use in High Risk Patients (Room D-1 (1F)) - Sep 24, 2024 - Abstract #ICBMT2024ICBMT_121;
The development of Haplo-identical stem cell transplantation by using post- transplant Cyclophosphamide and the much faster availability of an haplo-identical donor has led to an increase of haplo-identical donor cell transplantation and current ongoing studies address the question whether haplo-identical donor should be preferred to MUD. Sponsored by Merck MSD Korea
- |||||||||| Prevymis (letermovir) / Merck (MSD), Livtencity (maribavir) / Takeda, GSK
Review, Journal: Current Perspectives on Letermovir and Maribavir for the Management of Cytomegalovirus Infection in Solid Organ Transplant Recipients. (Pubmed Central) - Sep 11, 2024
For decades, CMV management after transplantation has relied on antiviral drugs that inhibit viral DNA polymerase (ganciclovir, foscarnet, and cidofovir)...However, letermovir and maribavir have a significant drug interaction potential in solid organ transplant recipients, resulting in higher levels of calcineurin inhibitors (cyclosporine and tacrolimus) and mTOR inhibitors (sirolimus and everolimus)...This article provides a comprehensive review of the clinical data supporting the use of letermovir and maribavir in clinical practice. The author provides perspectives on the role of these newly approved drugs in the current management landscape of CMV infection in solid organ transplantation.
- |||||||||| Review, Journal: Management of resistant and Refractory Cytomegalovirus infections after transplantation. (Pubmed Central) - Sep 3, 2024
This is likely the result of a combination of prolonged antiviral exposure and active viral replication in the setting of intense pharmacologic immunosuppression. Successful control of resistant and refractory infections in transplant recipients requires a combination of immunomodulatory optimization and appropriate antiviral drug choice with sufficient treatment duration.
- |||||||||| favipiravir / Generic mfg.
Journal: Convenient screening of the reproductive toxicity of favipiravir and antiviral drugs in Caenorhabditis elegans. (Pubmed Central) - Aug 21, 2024
The concordance between the results of the screening system for reproductive toxicity of antivirals in C. elegans and those in experimental animals based on the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, reproductive toxicology confirms its appropriateness as a screening system for reproductive toxicity. Favipiravir and zidovudine were the least toxic to C. e legans among the antiviral drugs examined.
- |||||||||| The Battle Against CMV in Transplant Patients: A Case of Antiviral Resistance (Exhibit Hall E) - Aug 20, 2024 - Abstract #ACG2024ACG_783;
Postoperatively, she was started on Tacrolimus, Prednisone, Mycophenolate, Valganciclovir, and Sulfamethoxazole-Trimethoprim...There are only three oral drugs: Valganciclovir, Maribavir, and Letermovir, and limited IV options: Ganciclovir, Foscarnet, and Cidofovir...Further research and comprehensive guidelines are necessary to advance CMV management in solid organ transplant patients. Figure: Timeline covering the progression of CMV colitis, the development of resistance and various management strategies to symptom resolution spanning over 9 months
- |||||||||| Prevymis (letermovir) / Merck (MSD)
Enrollment open: Letermovir (Prevymis) for CMV in Kidney and Pancreas Transplant Recipients (clinicaltrials.gov) - Aug 20, 2024
P3, N=90, Recruiting,
Figure: Timeline covering the progression of CMV colitis, the development of resistance and various management strategies to symptom resolution spanning over 9 months Not yet recruiting --> Recruiting
- |||||||||| Prevymis (letermovir) / Merck (MSD), Livtencity (maribavir) / Takeda, GSK
Review, Journal: Refractory/Resistant Cytomegalovirus Infection in Transplant Recipients: An Update. (Pubmed Central) - Jul 31, 2024
Novel anti-CMV therapies have been recently developed and introduced in clinical practice, which may improve the treatment of these infections. In this review, we summarize the treatment options for R/R CMV infections in adult hematopoietic cell transplant and solid organ transplant recipients, with a special focus on newly available antiviral agents with anti-CMV activity, including maribavir and letermovir.
- |||||||||| Prevymis (letermovir) / Merck (MSD)
Trial completion date, Trial primary completion date: Letermovir (Prevymis) for CMV in Kidney and Pancreas Transplant Recipients (clinicaltrials.gov) - Jul 31, 2024
P3, N=90, Not yet recruiting,
In this review, we summarize the treatment options for R/R CMV infections in adult hematopoietic cell transplant and solid organ transplant recipients, with a special focus on newly available antiviral agents with anti-CMV activity, including maribavir and letermovir. Trial completion date: Jun 2026 --> Sep 2026 | Trial primary completion date: Jun 2026 --> Sep 2026
- |||||||||| Prevymis (letermovir) / Merck (MSD)
PK/PD data, Review, Journal: Clinical Pharmacokinetics and Pharmacodynamics of Letermovir in Allogenic Hematopoietic Cell Transplantation. (Pubmed Central) - Jul 21, 2024
In particular, attention should be paid to the drug-drug interactions between letermovir and calcineurin inhibitors or azole antifungal agents, which are commonly used in patients undergoing hematopoietic cell transplantation. This article reviews and summarizes the clinical pharmacokinetics and pharmacodynamics of letermovir, focusing on patients undergoing hematopoietic cell transplantation, healthy individuals, and specific patient subsets.
- |||||||||| Prevymis (letermovir) / Merck (MSD), Valcyte (valganciclovir) / Roche, Mitsubishi Tanabe
Trial completion date, Trial initiation date, Trial primary completion date, Monotherapy: LUCY-1: Letermovir-based Dual Therapy for Treatment of Cytomegalovirus Infections (clinicaltrials.gov) - Jul 19, 2024
P3, N=80, Not yet recruiting,
Prospective studies are required to validate these findings. Trial completion date: Apr 2027 --> Jul 2027 | Initiation date: Apr 2024 --> Jul 2024 | Trial primary completion date: Apr 2027 --> Jul 2027
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