- |||||||||| Journal: Navigating Cytomegalovirus Retinitis in a Patient With Myelodysplastic Syndromes Transitioning to Acute Myeloid Leukemia Post Transplant: A Case Study. (Pubmed Central) - Mar 7, 2025
Six months after the transplant, AML relapse was treated with cladribine, cytarabine, granulocyte-colony-stimulating factor/filgrastim, and mitoxantrone (CLAG-M) and venetoclax, leading to measurable clearance of TP53 mutations to undetectable levels by NGS and reduction of CD34+ blasts from 25% to 0%...This case illustrates the aggressive nature of MDS-AML progression, the critical role of vigilant CMV surveillance, and the nuanced approach needed for treatment, balancing efficacy against potential side effects. The successful navigation of these complexities offers valuable insights for similar cases.
- |||||||||| Prevymis (letermovir) / Merck (MSD), Valcyte (valganciclovir) / Roche, Mitsubishi Tanabe, Livtencity (maribavir) / Takeda, GSK
Journal: Bridging the Gaps in CMV Management in Transplantation: Lessons From Resource-Limited Settings. (Pubmed Central) - Feb 21, 2025
Scientific and lived experience expert panel review of anti-EBV therapies selected four candidates with evidence for efficacy against EBV and acceptable safety and tolerability for potential use in phase III clinical trials for MS. No abstract available
- |||||||||| Cytovene (ganciclovir) / Roche, Livtencity (maribavir) / Takeda, GSK
Review, Journal: What intensivists need to know about cytomegalovirus infection in immunocompromised ICU patients. (Pubmed Central) - Feb 1, 2025
Accurate interpretation of nucleic acid load levels and careful evaluation of CMV's pathogenic role when it is found are critical. Further studies focusing specifically on CMV infection and disease in critically ill immunocompromised patients are needed to optimize management strategies.
- |||||||||| Livtencity (maribavir) / Takeda, GSK
Journal: The effective multiplicity of infection for HCMV depends on the activity of the cellular 20S proteasome. (Pubmed Central) - Jan 31, 2025
We demonstrate that disrupting these activities inhibits viral replication while likely supporting increased antiviral activity of the anti-HCMV agent, maribavir. Using a combination of live-cell imaging and computational tools, we discover that a subset of infected cells progresses to fulminant infection, which we define as the effective multiplicity of infection, and this subset would otherwise be missed when analyzing the average of the population.
- |||||||||| Simulect (basiliximab) / Novartis, Cytovene (ganciclovir) / Roche, Livtencity (maribavir) / Takeda, GSK
Kaposi Sarcoma in a Lung Transplant Recipient (Poster Hall) - Jan 19, 2025 - Abstract #ISHLT2025ISHLT_1299;
He received 1000 mg solumedrol and basiliximab induction and tacrolimus (goal 8-10 ug/L), mycophenolate mofetil (MMF) 1000 mg BID, and prednisone 10 mg daily maintenance immunosuppression.Three months after transplant, he underwent bronchoscopy with transbronchial biopsy, which showed A1 rejection...Lung function improved but he developed persistent ganciclovir-resistance CMV viremia (peak 1,190 UI/mL) requiring maribavir...He was treated with liposomal doxorubicin 20 mg/m^2, tacrolimus goal was reduced to 4-6 ug/L, he received IVIG repletion, and he started everolimus...Coinfection with CMV activates HHV-8 lytic replication in endothelial cells and fibroblasts. KS treatment, including liposomal doxorubicin and mTOR inhibitor initiation resulted in significant tumor response.
- |||||||||| Cytovene (ganciclovir) / Roche
Reversion of Val(ganciclovir)-Resistance Associated Mutation in Two SOT Patients with Mismatch Serostatus for CMV (D+/R-) (Poster Hall) - Jan 19, 2025 - Abstract #ISHLT2025ISHLT_454;
We present two cases report, both SOT mismatch for CMV serostatus (D+/R-), showing the reversion of UL97 mutations associated with val(ganciclovir) (VGCV) resistance.Case Report Patient 1: a 30-yr-old man with Danon disease received heart transplant in October 2021; due to the occurrence of multiple episodes of CMV infection in 2022 he was pre-emptively treated with VGCV and subsequently with foscarnet...He was finally treated with maribavir (MBV) in August 2022, when blood CMV DNA was 123,750 copies/ml and was suffering for CMV-associated colitis...After achieving CMV DNA suppression with MBV, the secondary prophylaxis was started with letermovir associated with VGCV...In the two reported cases, the reversion of VGCV-resistance associated mutations was observed after withdrawal of the drug. To our knowledge this observation has never been previously reported, and can be taken into account for the management of antiviral treatment of CMV infections in D+/R- SOT.
- |||||||||| Review, Journal: Advances and Prospect in Herpesviruses infections after Hematopoietic Cell Transplantation: Closer to the Finish Line? (Pubmed Central) - Dec 18, 2024
CMV-specific T lymphocyte infusions offers a promising therapeutic option, warranting further investigation. Although considerable advances have been achieved for the treatment and prevention of herpes virus infections, most notably with CMV, the coming years should hold additional opportunities to tame the beast in these herpesviruses postallogeneic HCT, with the advent of new antivirals, cell-mediated immunity testing, and cytotoxic T lymphocytes infusions.
- |||||||||| Livtencity (maribavir) / Takeda, GSK
P3 data, Journal: Maribavir for refractory cytomegalovirus infection (with or without resistance) in solid organ transplant recipients: subgroup analysis of the phase 3 randomized SOLSTICE study. (Pubmed Central) - Nov 30, 2024
P3
Although considerable advances have been achieved for the treatment and prevention of herpes virus infections, most notably with CMV, the coming years should hold additional opportunities to tame the beast in these herpesviruses postallogeneic HCT, with the advent of new antivirals, cell-mediated immunity testing, and cytotoxic T lymphocytes infusions. Consistent with findings in the overall SOLSTICE population, this subgroup analysis of SOT recipients demonstrated greater effectiveness of maribavir for cytomegalovirus viremia clearance and fewer discontinuations due to treatment-emergent adverse events than IAT.
- |||||||||| Livtencity (maribavir) / Takeda, GSK
Review, Journal: Maribavir treatment for resistant cytomegalovirus disseminated disease in kidney transplant recipients: A case-based scoping review of real life data in literature. (Pubmed Central) - Nov 25, 2024
A 54-year-old female with history of obesity, hypertension, and chronic kidney disease, on prednisone and tacrolimus after kidney transplantation in November 2022, soon after developed primary CMV infection, treated with Valganciclovir and CMV Ig...Due to slow decrease serum CMV-DNA and detection of UL97 mutation, conferring resistance to valganciclovir and ganciclovir, the patient was started on foscarnet and letermovir...For mild to moderate CMV disease, as with the cases reported in our review, or for proven ganciclovir, foscarnet or cidofovir resistance, MBV could be a valuable option...MBV was generally well-tolerated, with low rates of toxicity, normally reversible. The introduction of new oral antivirals, such as MBV, could improve treatment, prophylaxis and preemptive treatment strategies, especially in anti-CMV treatment experienced patients.
- |||||||||| Livtencity (maribavir) / Takeda, GSK
PK/PD data, Journal: Population pharmacokinetics and exposure-response relationships of maribavir in transplant recipients with cytomegalovirus infection. (Pubmed Central) - Nov 20, 2024
A statistically significant association with maribavir exposure was identified for taste disturbance, fatigue, and treatment-emergent serious adverse events, while transplant type, enrollment region, CMV DNA level at baseline, and/or CMV resistance at baseline were identified as additional risk factors for these safety outcomes. In conclusion, the findings of these PopPK and exposure-response analyses provide further support for the recommended maribavir dose of 400
- |||||||||| 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.
- |||||||||| Livtencity (maribavir) / Takeda, GSK
The Cost-Effectiveness of Maribavir for Post-Transplant Refractory Cytomegalovirus Infection in France () - Nov 4, 2024 - Abstract #ISPOREU2024ISPOR_EU_1642;
P3
This study aims to estimate the cost-effectiveness of maribavir versus investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) which is the current standard of care for the treatment of refractory CMV infection post-transplant in France. These economic analyses indicate that maribavir is cost-effective in France compared with alternative anti-CMV therapies for the treatment patients with post-tranplant refractory CMV infection.
- |||||||||| Livtencity (maribavir) / Takeda, GSK
Journal: The effective multiplicity of infection for HCMV depends on activity of the cellular 20S proteasome. (Pubmed Central) - Nov 1, 2024
We demonstrate that disrupting these activities inhibits viral replication while likely supporting increased antiviral activity of the anti-HCMV agent, maribavir. Using a combination of live cell imaging and computational tools, we discover that a subset of infected cells progresses to fulminant infection which we define as the effective MOI, and this subset would otherwise be missed when analyzing the average of the population.
- |||||||||| Livtencity (maribavir) / Takeda, GSK
Enrollment open, Post-transplantation: A Study of Maribavir in Adults With Post-transplant Cytomegalovirus (CMV) Infection in Argentina (clinicaltrials.gov) - Oct 17, 2024
P=N/A, N=10, Recruiting,
Using a combination of live cell imaging and computational tools, we discover that a subset of infected cells progresses to fulminant infection which we define as the effective MOI, and this subset would otherwise be missed when analyzing the average of the population. Not yet recruiting --> Recruiting
- |||||||||| Valcyte (valganciclovir) / Roche, Mitsubishi Tanabe, Cytovene (ganciclovir) / Roche, Livtencity (maribavir) / Takeda, GSK
Review, Journal: Cytomegalovirus infection in gastroenterology (Pubmed Central) - Oct 15, 2024
Recruiting --> Active, not recruiting Timely identification of risk factors for the development of CMV infection, the introduction of innovative methods and approaches in diagnosis, and the use of effective methods for treating diseases of the digestive system associated with CMV infection can improve the prognosis of the underlying disease and reduce the risk of developing urgent conditions in gastroenterology.
- |||||||||| Valcyte (valganciclovir) / Roche, Mitsubishi Tanabe, Livtencity (maribavir) / Takeda, GSK
The Silent Invader, Cytomegalovirus Nephritis: A Rare Presentation in Early Post-transplant Period () - Oct 12, 2024 - Abstract #KIDNEYWEEK2024KIDNEY_WEEK_5466;
He was maintained on valgancyclovir prophylaxis dosed per eGFR for CMV HR...As per infectious disease recommendations, he was treated with Maribavir 400mg BID x 8 weeks for refractory CMV nephritis and immunosuppression was lowered...His ABMR was likely an unintended consequence of decreasing immunosuppression during treatment of CMV nephritis. Appropriate prophylaxis and early detection of CMV infection is particularly important in CMV HR transplant patients..
- |||||||||| Prevymis (letermovir) / Merck (MSD), Livtencity (maribavir) / Takeda, GSK
Journal, Real-world evidence, Real-world: The emergence of letermovir and maribavir drug-resistant mutations: from clinical trials to real-world studies. (Pubmed Central) - Sep 27, 2024
In summary, these novel data provide evidence for the importance of CDK8 as a positive regulator of herpesviral replication efficiency, and moreover, suggest its exploitability as an antiviral target for novel strategies of host-directed drug development. The detection of letermovir and maribavir resistance mutations highlights an ongoing clinical challenge in the management of CMV.
- |||||||||| 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.
- |||||||||| 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), 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.
- |||||||||| Livtencity (maribavir) / Takeda, GSK
Review, Journal: Understanding the Cytomegalovirus Cyclin-Dependent Kinase Ortholog pUL97 as a Multifaceted Regulator and an Antiviral Drug Target. (Pubmed Central) - Aug 28, 2024
Importantly, a statistically significant drug synergy has recently been reported for antiviral treatment schemes using combinations of pharmacologically relevant CDK7 and vCDK/pUL97 inhibitors, including maribavir...This review focuses on regulatory interactions of vCDK/pUL97 with the host cyclin-CDK apparatus, and it addresses the functional relevance of these key effector complexes for viral replication and pathogenesis. On this basis, novel strategies of antiviral drug targeting are defined.
- |||||||||| 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
|
