- |||||||||| Prevymis (letermovir) / Merck (MSD), Noxafil (posaconazole) / Merck (MSD), Cresemba (isavuconazonium sulfate) / Astellas, Basilea
A Quality Improvement Project to Coordinate Expensive, Difficult-to-Obtain, Prophylactic Medications before Discharge in an Academic Stem Cell Transplant Unit: 10 Month Results (HCC Exhibit Hall 3; In-Person) - Dec 19, 2024 - Abstract #TCTASTCTCIBMTR2025TCT_ASTCT_CIBMTR_1316;
Conclusion : PDSA cycle 1 successfully reduced TTAM, process variation, and the percentage of patients discharged without medications in hand (2.3%) surpassing our aim. Next steps include examining our free drug program process as a separate process measure, demonstrating ongoing sustainability of the new process, and a survey requesting feedback to identify balance measures.
- |||||||||| Prevymis (letermovir) / Merck (MSD)
Heterogeneity of Survival Benefit Derived from Letermovir: Linear Regression and Machine Learning Approaches (HCC Exhibit Hall 3; In-Person) - Dec 19, 2024 - Abstract #TCTASTCTCIBMTR2025TCT_ASTCT_CIBMTR_1158;
In contrast, more than 50% of patients with PTCy Haplo were considered low benefit by the ML model. In conclusion, our models succeeded in extracting patients expected to have lower NRM when we applied LTV as prophylaxis, supporting the hypothesis that survival benefits from LTV vary based on baseline characteristics.
- |||||||||| Prevymis (letermovir) / Merck (MSD)
Letermovir Prophylaxis in Cytomegalovirus Seronegative Recipients with a Seropositive Donor Allogeneic Hematopoietic Cell Transplant: A Single-Center Experience (HCC Exhibit Hall 3; In-Person) - Dec 19, 2024 - Abstract #TCTASTCTCIBMTR2025TCT_ASTCT_CIBMTR_830;
Letermovir (LTV) is effective at reducing clinically significant CMV infection (CS-CMVi) in CMV-seropositive patients, including among those with risk factors such as post-transplant cyclophosphamide (PTCy)...Immunosuppression at the time of CS-CMVi included tacrolimus (n = 15, 83%), prednisone (n = 12, 67%), and ruxolitinib (n = 2, 11%)...Conclusion This study did not find a significant reduction in CS-CMVi among D+/R- HCT patients who received LTV but is limited by a small sample size. Prospective studies are needed to determine if D+/R- HCT patients benefit from primary prophylaxis with LTV.
- |||||||||| Review, Journal: Advances and Prospect in Herpesviruses infections after Hematopoietic Cell Transplantation: Closer to the Finish Line? (Pubmed Central) - Dec 18, 2024
Prospective studies are needed to determine if D+/R- HCT patients benefit from primary prophylaxis with LTV. 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.
- |||||||||| Prevymis (letermovir) / Merck (MSD)
Journal, Post-transplantation: Lin A, Brown S, Chinapen S, et (Pubmed Central) - Dec 12, 2024
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. No abstract available
- |||||||||| Prevymis (letermovir) / Merck (MSD), Valcyte (valganciclovir) / Roche, Mitsubishi Tanabe
Journal: Multiple Anterior Chamber Paracenteses May Be Needed to Identify Cytomegalovirus Anterior Uveitis. (Pubmed Central) - Dec 11, 2024
Clinicians should maintain a high index of suspicion for CMV in cases of recurrent anterior uveitis, particularly in patients of East and Southeast Asian descent. This study highlights the importance of repeated testing and appropriate antiviral treatment to prevent complications such as glaucoma.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
Ptcy Versus High Dose of ATG in HLA-Mismatched Unrelated Stem Cell Transplantation for Hematological Malignancies () - Dec 7, 2024 - Abstract #ASH2024ASH_9370;
Retrospective studies suggest PTCY may offer better outcomes than rabbit anti-thymocyte globulin (ATG), potentially due to lower NRM and GVHD rates...Patients received high-dose ATG (HD group : ATG-T 10 mg/kg or ATG-F 60 mg/kg), low-dose ATG (LD group : ATG-T 5 mg/kg or ATG-F 30 mg/kg), or PTCY (PTCY 50mg/kg at day +3 and +4) as GVHD prophylaxis, along with cyclosporin and methotrexate or mycophenolate mofetil.A total of 155 patients were included (41 in the PTCY group, 93 in the HD group, and 21 in the LD group), with median follow-ups of 15.2, 16.23, and 22.5 months, respectively...However, the PTCY group exhibited lower infection rates and GVHD-related mortality, even if we cannot exclude the impact of more recently introduced anti-infectious prophylaxis such as letermovir. These results suggest that PTCY provides added value as GVHD prophylaxis in MMUD alloSCT.
- |||||||||| Prevymis (letermovir) / Merck (MSD)
Outcomes of 9/10 Mmud Allo-HCT Using Ptcy-TK Prophylaxis. Results from a Single Institution () - Dec 7, 2024 - Abstract #ASH2024ASH_9369;
In 2013, our institution implemented the use of PTCY combined with tacrolimus (TK) and mycophenolate mofetil (MMF) (PTCY-TK-MMF) for MMUD peripheral blood (PB) allo-HCT with notable success...However, since letermovir prophylaxisimplementation in 2021, only 1 (5.8%) patient had CMV reactivation and it occurred after its discontinuation.The Cum.Inc of grades II-IV and III-IV acute GVHD (aGVHD) at day +100 and moderate/severe chronic GVHD (cGVHD) at 2 years were 33.0%, 9.7%, and 12.6%, respectively...The 3-year overall survival (OS), non-relapse mortality (NRM), and cumulative incidence of relapse (CIR) were 61.8%, 22.9%, and 22.3%, respectively.The impact of HLA disparity on outcomes was investigated according to class I or II donor/recipient HLA-mismatch, showing that when using PTCY-based prophylaxis, the infusion of class I HLA MMUD products did not significantly impact outcomes (1-year NRM : 20.3% vs. 15.9%, P=0.842 / 1-year CIR : 12.4% vs. 36.5%, P=0.075 / 1-year OS : 70.7% vs. 62.9%, P=0.473) and GVHD incidences; although rates of moderate/severe cGVHD were lower in patients who received class II MMUD products (day +100 grades II-IV : 32.6% vs. 35.7%, P=0.839 / grades III-IV : 10.1% vs. 7.1%, P=0.74 / and 2-year mod/sev cGVHD : 14.8% vs. 0, P=0.153).CONCLUSIONOur data support the use of dual GVHD prophylaxis composed of PTCY-TK in MMUD allo-HCT, demonstrating satisfactory GVHD prevention and survival rates. Notably, the infusion of class I HLA MMUD products did not significantly impact outcomes when using PTCY-based prophylaxis.
- |||||||||| Prevymis (letermovir) / Merck (MSD)
Letermovir Prophylaxis Is Effective in Preventing CMV Reactivation and Is Associated with Decreased Non-Relapse Mortality in Two-Step Allogeneic Stem Cell Transplantation () - Dec 7, 2024 - Abstract #ASH2024ASH_9346;
The hazard ratio for CMV infection was 0.34 (95% CI, .13 to .66; P = .003) in patients who received primary prophylaxis with letermovir.The 1-year cumulative incidence of NRM was lower in at risk patients with letermovir prophylaxis compared to those without prophylaxis (11.9% versus 26.1%, p-value < 0.05). Overall survival (74.3% versus 69.3%) and progression-free survival (70.9% versus 69.6%) were similar between the two groups.ConclusionOur results indicate that letermovir is effective in preventing early and late CMV reactivation and is associated with decreased NRM in high-risk patients who undergo transplantation using the 2-step alloHSCT.
- |||||||||| Prevymis (letermovir) / Merck (MSD)
Real-World Safety and Effectiveness of Letermovir in Pediatric Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation () - Dec 7, 2024 - Abstract #ASH2024ASH_9323;
The average engraftment of neutrophil between the two was 13.0 days vs 12.2 days (P=0.046), the average engraftment of platelet was 13.8 days vs 12.5 days (P=0.120), and all the patients received letermovir were with no serious adverse events.Conclusions : Letermovir as prophylactic treatment after allo-HSCT reduce the CMV reactivation, delay the time to CMV reactivation, and reduce the peak CMV copy number in pediatric patients, which may affect the engraftment time of neutrophil but does not cause the failure of engraftment or serious adverse events. Letermovir may also reduce CMV reactivation and peak value after cord blood transplantation, but larger sample data are needed to support it.This study confirms the effectiveness and safety of letermovir for CMV prophylaxis in pediatric patients undergoing allo-HSCT in real-world settings.
- |||||||||| Prevymis (letermovir) / Merck (MSD)
Letermovir Primary Prophylaxis in Preventing Cytomegalovirus (CMV) Reactivation in Ex-Vivo Tcr??-Depleted Haploidentical Allogeneic Haematopoietic Cell Transplantation with Memory T Cell Add-Back () - Dec 7, 2024 - Abstract #ASH2024ASH_9307;
Notably, the impact of LET prophylaxis remained significant on OS (HR 0.36, 95% CI 0.19-0.69; p=0.002), EFS (HR 0.44, 95% CI 0.25-0.77; p=0.004) and NRM (HR 0.30, 95% CI 0.13-0.72; p=0.007) in the multivariate analyses.CONCLUSIONAs compared to PET strategy, LET prophylaxis effectively reduced the risk of CMV infection in our high-risk patients undergoing ex vivo T-cell-depleted haplo-HCT, and was associated with reduced non-relapse mortality and improved overall and event-free survival. Delayed CMV infection remains a major concern, further studies are needed to identify subgroup of patients who may benefit from extended letermovir prophylaxis.No conflict of interest to disclose.
- |||||||||| Prevymis (letermovir) / Merck (MSD), Cytovene (ganciclovir) / Roche, Rituxan (rituximab) / Roche
New Insights in Current Practice in the Management of DNA Viruses in Children Following Allogeneic HSCT at EBMT Centers () - Dec 7, 2024 - Abstract #ASH2024ASH_9302;
RTX is considered for use as EBV prophylaxis mostly in haplo HSCT settings. Addressing the causes of deviations from guidelines in routine practice may help improve the management of these viruses.*On Behalf of the European Society for Blood and Marrow Transplan tation (EBMT) Infectious Diseases Working Party (IDWP) and Pediatric Diseases Working Party (PDWP).
- |||||||||| Prevymis (letermovir) / Merck (MSD), Ovastat (treosulfan) / Medac, Medexus, Rituxan (rituximab) / Roche
Donor-Derived NK Cell Infusion Following Haploidentical Hematopoietic Stem Cell Transplant for High-Risk and Relapsed/Refractory Pediatric Leukemia () - Dec 7, 2024 - Abstract #ASH2024ASH_9219;
Infusion of mature donor NK cells could be useful in patients undergoing haplo-HSCT, ensuring control of disease and viral reactivations, before and during engraftment in the recipient.Patients and MethodsWe evaluated the outcome of 5 pediatric patients with high-risk leukemia who were planned to receive haplo-HSCT with donor NK cells infusion following one of two different conditioning platforms, Post-Transplant Cyclophosphamide (PTCy) and T-??/B cell-depleted...Conditioning regimen consisted of Busulfan/Treosulfan + Fludarabine and Thiotepa backbone for 4 patients; 1 patient received TBI...Patients who underwent T ??/B cells depletion haplo-HSCT received rituximab and letermovir for EBV and CMV prophylaxis, respectively...Mild, steroid-responsive acute GvHD was observed and limited chronic GvHD. These limited but very promising preliminary results need to be confirmed in larger cohorts.
- |||||||||| Prevymis (letermovir) / Merck (MSD)
Review, Journal: SOHO State of the Art Updates and Next Questions | Current Status and Future Directions of Donor Selection. (Pubmed Central) - Nov 27, 2024
Selecting a cytomegalovirus (CMV) seronegative donor is important particularly for CMV-negative recipients; however, more research is needed in the letermovir prophylaxis era...Future research addressing these issues will refine donor selection algorithms and improve transplant success. In conclusion, selecting a donor for HCT requires multifaceted considerations, integrating evolving HLA-matching criteria and non-HLA factors, to optimize HCT outcomes in this rapidly advancing field.
- |||||||||| 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.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
Steroid Pre-Busulfan Based Reduced-Intensity Conditioning in Matched Related Hematopoietic Stem Cell Transplantation: Outcomes in Young and Adult Sickle Cell Disease Patients (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_6621;
All patients underwent a uniform reduced intensity conditioning (RIC) regimen comprising fludarabine, antithymocyte globulin and intravenous busulfan (Flu/r-ATG/IV-Bu)...Graft-versus-host disease (GVHD) prophylaxis utilized either Cyclosporine A/Methotrexate (57.4%, n=66) or Tacrolimus/Methotrexate (42.6%, n=49)...The favorable outcomes may be attributed, in part, to our pre-transplant conditioning regimen, which included a 4-week course of alternate-day prednisone...The recent approval of Letermovir for CMV prophylaxis is likely to decrease the risk of post-transplant CMV viremia. These findings may significantly impact treatment paradigms for young and adult SCD patients, offering hope for a curative option to a broader patient population.
- |||||||||| Prevymis (letermovir) / Merck (MSD), Vistide (cidofovir) / Gilead
CD7.Pebl-CART for Patients with Relapsed/Refractory (r/r) T-Cell Acute Lymphoblastic Leukemia (T-ALL) (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3847;
P1/2
BK virus infection causing hemorrhagic cystitis occurred in 2 patients, and CMV reactivation in 1 patient (successfully treated with foscarnet)...The role of allo-HSCT as consolidation remains to be determined. A phase I/II clinical trial to confirm these promising results is active and currently enrolling at our Institution (NCT06064903).
- |||||||||| Prevymis (letermovir) / Merck (MSD)
Early CMV Viral Load Burden Predicts Late Clinically Significant CMV Infections in Patients Receiving Ptcy-Based Hematopoietic Cell Transplantation (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3360;
Here, we show that patients with the highest burden of CMV viremia in the first 100 days after transplant, had the highest risk of late CS-CMVi after D100, while patients with no viremia in the first 100 days had the lowest risk of late CS-CMVi, demonstrating that in the setting of PTCy-based GvHD prophylaxis including those receiving letermovir prophylaxis, the CMV AUC is an additional tool to stratify patients at risk for late CS-CMVi. In addition, while some studies have suggested that early low-grade viremia is important for establishing CMV-specific immunity and protection from late CMV infections, we did not find that in this cohort of recipients of PTCy-based HCT.
- |||||||||| Prevymis (letermovir) / Merck (MSD)
Appropriate Threshold of Quantitative Cytomegalovirus DNA Polymerase Chain Reaction for Preemptive Treatment in Stem Cell Transplant Recipients (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3345;
There were only 9 low-risk patients with letermovir, but a threshold similar to that for low-risk patients without letermovir seemed appropriate. Conclusion For high-risk patients with or without letermovir, a threshold of 50 IU/ml and 150 IU/ml, respectively, may be recommended, while a threshold of 500-750 IU/ml may be proposed for low-risk patients, to decrease the overuse of antiviral agents with minimal delay in preemptive treatment.
- |||||||||| Prevymis (letermovir) / Merck (MSD), Actemra IV (tocilizumab) / Roche, JW Pharma
Expression of HLA-B*35 Is Associated with an Increased Risk of CMV Viremia and Clinically Significant CMV Infection in Patients Receiving Ptcy-Based Hematopoietic Cell Transplantation (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3341;
Introduction : Hematopoietic cell transplant (HCT) with post-transplant cyclophosphamide (PTCy) graft-versus-host disease (GvHD) prophylaxis is associated with an increased risk of cytomegalovirus (CMV) infections despite widespread use of prophylactic letermovir...Tested covariates included age, sex, disease, HCT-CI, donor sex, donor match, letermovir use, CMV recipient and donor seropositivity, conditioning intensity, graft type, CD34+ cell dose, tocilizumab use, recipient HLA-B*35 positivity, and donor HLA-B*35 positivity...Discussion : In this study, HLA-B*35 recipient positivity was associated with an increased risk of CMV viremia and CS-CMVi suggesting a possible defect in CMV antigen presentation by HLA-B*35 bearing targets that may represent a novel tool to identify patients at risk of post-HCT CMV infection despite letermovir use. Future studies are needed to elucidate the mechanism and investigate how this may be used to identify and optimally manage patients at highest risk for CMV infections after HCT.
- |||||||||| Prevymis (letermovir) / Merck (MSD)
Donor Chimerism Monitorization for Relapse Prediction in Ex-Vivo CD34-Selected Allogenic Hematopoietic Stem Cell Transplant (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3293;
Baseline characteristics (including CD3 cells infused, intensity conditioning, HLA mismatch, CMV serology mismatch and letermovir prophylaxis) in both groups were comparable...In our cohort, persistence of MC in TL along the post CD34S-HSCT long period does not seem to confer a negative impact on disease relapse or survival. Early intervention based only on MC behavior would not be necessary.
- |||||||||| 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.
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