What is the recommended approach for Cytomegalovirus (CMV) prophylaxis in high-risk populations?

CMV Prophylaxis in High-Risk Populations

For high-risk populations, letermovir is recommended as primary prophylaxis for CMV-seropositive allogeneic hematopoietic cell transplant (HCT) recipients, while a preemptive strategy with weekly CMV viral load monitoring is recommended for other high-risk groups. 1

Risk Stratification for CMV Prophylaxis

Highest Risk Populations

• Allogeneic HCT recipients who are CMV seropositive 1
• CMV-seronegative recipients receiving organs from CMV-seropositive donors (D+/R-) 1, 2
• Patients receiving alemtuzumab or other T-cell depleting therapies 1

Prophylactic Approaches by Risk Group

For Allogeneic HCT Recipients

• Primary prophylaxis with letermovir (480 mg/day orally or IV, or 240 mg/day if taking cyclosporine) is recommended for CMV-seropositive recipients 1
• Letermovir should be administered through day 100 post-HCT, with consideration for extension to day 200 in high-risk patients 1
• Letermovir lacks HSV and VZV coverage, so concurrent HSV/VZV prophylaxis should be continued 1

For Solid Organ Transplant Recipients (D+/R-)

• Valganciclovir 900 mg once daily for 200 days post-transplant is superior to 100 days of prophylaxis in kidney transplant recipients 2, 3
• Extended prophylaxis (200 days) significantly reduces CMV disease incidence compared to standard 100-day prophylaxis (16.1% vs. 36.8%, p<0.0001) 3
• Number needed to treat to prevent one case of CMV disease is approximately 5 patients 3

Preemptive Therapy Approach

• Weekly quantitative CMV viral load monitoring by PCR for at least 3-6 months post-transplant in high-risk patients 1
• Initiate preemptive therapy upon detection of CMV viremia with: 1
  • Valganciclovir (PO) or
  • Ganciclovir (IV) or
  • Foscarnet (IV) in cases of ganciclovir intolerance or resistance
• Continue therapy for at least 2 weeks and until CMV is no longer detected 1

Special Considerations

For Alemtuzumab Recipients

• CMV monitoring and preemptive therapy for a minimum of 2 months after alemtuzumab therapy 1
• Continue monitoring until CD4+ cell counts reach ≥200 cells/mcL 1

For Patients with Chronic GVHD

• Extended prophylaxis may be considered in patients with severe chronic GVHD, intensive glucocorticoid therapy, or after T-cell depletion 1
• Prolonged monitoring for up to 1 year after transplantation is recommended 1

Medication Selection and Dosing

Antiviral Options

• Letermovir: Preferred for prophylaxis in allogeneic HCT recipients due to lower toxicity profile 1
• Valganciclovir: 900 mg once daily for prophylaxis in solid organ transplant recipients 2, 3
• Ganciclovir: IV option for patients with absorption issues 1
• Foscarnet: Alternative for patients with ganciclovir resistance or intolerance 1

Medication Considerations

• Ganciclovir and valganciclovir can cause bone marrow suppression 1
• Foscarnet can cause nephrotoxicity and electrolyte abnormalities 1
• Cidofovir is associated with substantial nephrotoxicity and potential ocular toxicity 1
• Acyclovir and valacyclovir are only weakly active against CMV and not recommended for CMV prophylaxis 1

Common Pitfalls and Caveats

• Rapid emergence of resistant mutants can occur with letermovir if treatment is interrupted or underdosed 1
• Late-onset CMV disease can occur after discontinuation of prophylaxis, necessitating continued vigilance 3
• CMV-negative patients with CMV-negative donors should receive only CMV-negative and/or filtered blood products 1
• Prophylactic immunoglobulin administration is generally not recommended except in limited situations due to cost and limited evidence of activity 1
• Intravenous immunoglobulin (IVIG) may be considered as adjunctive therapy for CMV pneumonitis but is not routinely recommended for prophylaxis 1