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Madeleine R. Heldman, MD, MS, Discussions Managing Cytomegalovirus, Including Advances in CMV Assessment and Antiviral and Imamune Strategies.
CLINICAL TRIAL RESULTS OVER THE PAST 5 YEARS HAVE ENABLED NEW APPROACHES TO CYTOMEGALOVIRUS PREVENTION IN TRANSPLANTATION SETTINGS, RESEARCHERS WROTE IN THEIR REVIEW OF CURRENT AND FUTURE STRATEGIES TO PREVENT AND TREAT CMV INFECTIONS IN TRANSLANTS.
“Letermovir and Maribavir Are New Antivirals for the Prevention and Treatment of CMV Infections, respective, and are Safe Alternativates to Historical Agents. Investigational Strategies That Enhance Cmv Immunity Have Potential To Improve Long-Term Cmv Control in Different Transplant Settings, ”They added in Clinical infectious disseeses.
However, The Researchers ADVISED THAT PREVENTING AND TREATING CMV Infection is an Important Aspect of Clinical Care in Solid Organ and Allogeneic Hematopoietic Cell Transplantation, and More Studies Are Needed to Refine Their Use.
They Review Recent Advances in CMV Risk Assessment and Progress in Antiviral and Imamune-Based Strategies to Prevent and Treat CMV, Emphasizing CMV-Specific immunity through vaccination, Monoclonal Antibodies, and Virus-Specific T-Cells. They also Summarized Observational and Interventional Studies of Commercially Available CMV Cell-Mediated Immunity Assays.
Lead Author Madeleine R. Heldman, MD, MSspoke with Physician’s Weekly (Pw) About the Results of Their Review.
PW: For Clinicians, what are the review’s key points?
Dr. Heldman: Cmv is one of the most common infections in transplant recipients and causes a lot of anxiety for patients and clinicians. In the Past 5 Years, We Have Seen Two New Antivirals, Letermovir and Maribavir, Becoma Available for CMV Prevention and Treatment, respective. These are oral Drugs with Fewer toxicities Than historical antivirals.
While the advent of these novel agents is exciting, antivirals of not address the deficits in cmv-specific immares replies that underlie the predisposition to cmv infections after transplant. Vaccines, Monoclonal Antibodies, and Virus-Specific T Cells aremune-Based Strategies That Are Activery Being Evaluated in Clinical Trials.
Why Was It Important To Conduct This Review?
The epidemiology of transplant recipients at risk for cmv is evolving. In Solid Organ Transplant (SOT), CMV SERONEGATIVE RECIPIES OF ORGANS FROM CMV SEROPOSITIVE OWNERS (D+R-) ACCOUNT FOR APPROXIMATELY 20% OF ALL SOT RECIPIES BUT FOR OVER 90% OF CASES OF CMV Disease (IE, CMV INFECTION THAT ILLNESS). The PROPHORTION OF SOTS THAT ARE CMV D+R- HAS INCREASED OVER THE PAST DECADE AND IS PROJECTED TO CONTINUE INCREASING IF CURRENT TREDS CONTINUE.
In Hematopoietic Cell Transplant (HCT), Post-Transplant Cyclophosphamide (PTCY) Is Increasingly Used for Graft-Versus-Disest Disease Prevention, and the Landscape of CMV Infections After Ptcy Will Need to Be Explored. Commercial Assays That Measure CMV-Specific Cell-Mediated Immunity Are Becoming Available, and Clinicians Should Understand How they predictive Vary in Different Transplant Population.
Did the Results You Reviewed Surprized You?
We Discussed Findings From Recent Studies That Are Not Necessary Intuitive. Pre-Emptive Therapy (Pet) and Prophylaxis Are Established Strategies for Preventing CMV Disease In Sot Reciers. Pet Involves Weekly CMV PCR Surveillance and Only Initating CMV Antivirals for Treatment at Pre-Defined Viral Load Thresholds. Many Centers Using Prophylaxis over Pet in High-Risk CMV D+R-SOT RECIPIES, Given the Rapid Kinetics of CMV Replication in This Population and Theoretical Concerns About The Potential Effects of Asymplantic CMV Infection on Long-Term Graft Survival and Outcomes.
We Discussed a randomized clinical trial that compred pet to valganciclovir prophylaxis for the prevention of cmv dissease in cmv d+r- liver transplant recipients. Pet was actually superior to prophylaxis in preventing cmv dissease in the first year year after transplant. Immunologic Studies Suggest That the Early, Controlled Dnaemia Intrinsic to Pet Facilitates Development of CMV-Specific Imamune Responses, Which Ultimately Protects Pats from Late CMV Infections.
What are your Thoughts on Advances in CMV Risk Assessment and Treatment and Differences in CMV Management Based on Transplant Type (Solid Organ vs. Stem Cell)?
The Risks and Benefits of Any CMV Prevention or Treatment Strategy Differ Consideirably Betweeen Sot and HCT and by Over and RECIPIENT SEROSTATUS, IMMUNOSUPPRESSION, Hematopoietic Cell Source and Hla Matching (HCT), and Organ Type (SOT).
Another Important Difference Between Sot and HCT is that hct recipients may eventually Develop to “Normal” Imamune System (In the Absence of Relationis Diseed Disease or Chronic Graft versus Host Disease). SOT RECAPINES REQUIRE LIFELONG IMMUNINOSUPPRESSION.
This means that antiviral prophylaxis for a fixed duration after hct may be a sufficient “bridge” to immares reconstitution. In Sot, Antiviral Prophylaxis May Simply Delay Inevitable CMV Infection in Some Patients.
Are Any Strengths or Limitations of the Review Specially Noteworthy?
The Strengths and Limitations of All Interventions Discussed in the Review Can Differ Consideirably in Different Transplant Population. Example, CMV-SPECIFIC CELL-MEDIATED IMMUNITY ASSAYS HAVE BETTER PREDICTIVE VALUE IN CMV SEROPOSITIVE (R+) SOT RECIPIES THAN CMV D+R- SOT RECIPIES, ALTHUNT CMV D+R- PATIENTS HAVE THE HIGHHEST CMV-REALLED MORBDITY AND COULD BENEFIT Accurate CMV Imamune Assessments. PET WAS SAFE AND EFFICIOUS IN A RANDOMIZED CLINICAL TRIAL IN CMV D+R-LIVER RECIPIES, But it has not Been Systemicically Evaluated in Oter D+R-SOT POPULATIONS. ORGAN-SPECIFIC FACTORS AND DIFFERENCES IN IMMUMNOSUPPRESSION BETZEN DIFFERENT ORGAN GROUPS IFRUDE EXTRAPOLATION TO NON-LIVER SOT POPULATIONS.
What Further Research is Needed?
Alleviating The Financial Toxicity and Inconvenience of Anti-CMV Medications and Laboratory Testing is an Important Aspect of Everyday Patient Care. Studies Are Underway That Will Assess the Feasability and Accuracy of At-Home Blood Collection for CMV PCR Testing (EG, Dried Blood Spot Testing and Self-Mustan Devices). These Methods Could Facilitate Tight CMV PCR Surveillance for High-Risk Patients Who Live Far From Their Transplant Centers. Vaccines are another potential avenue toward reducing reliance on antivirals.
An Ongoing Randomized Clinical Trial Studying A (Non-Live) MVA-Vactored CMV Vaccine in CMV Seronegative Liver Transplant Candidates Will Yield Exciting Data in the Coming Decade.
What AddiThe Comments Willd You Like To Share With Clinicians?
CMV Management in Transplant Recipients is a multidisciplinary process. Successful CMV Prevention and Treatment Requires Physicians to Work with Pharmacists, Transplant Coordinators, and Case Managers to Ensure Access to Antivirals and Adherence to CMV Monitoring Schedules.
