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Optimal Strategy for CMV Prevention in HCT

CE / CME

Reducing the Burden of Cytomegalovirus in HCT: Optimal Strategy for Prevention

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Nurse Practitioners: 1.00 Nursing contact hours, includes 1.00 hour of pharmacotherapy credit

Released: July 21, 2023

Expiration: July 20, 2024

CME/CE Information

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Pros and Cons of Prophylaxis Strategy

There are many positives associated with using letermovir for primary prophylaxis of patients undergoing allo-HCT. As noted previously, this strategy improves survival in CMV-seropositive transplant recipients, and reduces risk for CMV disease and development of resistant or refractory infection.10,22,23,25 However, 1 caveat with letermovir use is that it is effective only against CMV, and not effective against herpes simplex virus (HSV) or varicella zoster virus (VZV); additional prophylaxis with acyclovir may be needed.7,21 

Myelotoxicity with ganciclovir or valganciclovir makes primary prophylaxis a less effective choice, as this toxicity may limit efficacy due to dose adjustments or treatment interruptions.20 

Prophylactic vs PET strategies also may delay reconstitution of CMV-specific immunity, which tends to recover more quickly with PET.10,20 Further, any prophylactic strategy includes the risk for unnecessary use of antivirals, which is balanced by improved survival. As the strategy evolves with newer options, a risk-based approach may mitigate the concern about excess antiviral use.27

Current guidelines from ASTCT and the National Comprehensive Cancer Network recommend prophylaxis with letermovir, particularly in seropositive recipients. Prophylaxis should begin within 28 days of transplantation and continue through Day 100 or longer, depending on patient factors.7,36 

Factors that can help guide CMV-related decision-making are listed in Table  4.6 Patients who receive letermovir (or other) prophylaxis and develop CMV infection usually are managed with a PET strategy. 

Table 4. Factors to Consider in CMV-Related Decision-making6

Whichever strategy is chosen, patient engagement is key to its success. Engaged patients who are informed and involved in decision-making are more likely to accept the rigors of treatment. Patients and their caregivers should be educated about the impact of CMV infection, the rationale for PET or prophylaxis, its requirements, and expected toxicities. 

Patient preference for oral vs IV therapy is a consideration. Letermovir is available orally and intravenously; ganciclovir is administered intravenously once or twice daily, requiring venous access. Valganciclovir is an oral drug with twice-daily dosing. For PET, patients must be available for qPCR monitoring weekly for at least 3 months after their procedure, and willing to accept therapy if CMV reactivation is detected. Those treated with oral agents need understanding of the importance of adherence to treatment efficacy, and strategies to support adherence. Education on expected toxicities and differentiating those requiring intervention can help to avoid treatment discontinuation due to mild or moderate nausea or gastrointestinal distress. However, treatment absorption may be decreased if severe vomiting or diarrhea occur. Patients should know to contact their healthcare team in the event of severe vomiting or diarrhea.

A successful outcome is more likely if education about CMV disease prevention is presented as an integral part of the HCT procedure and included prior to the transplant itself. 

Expert Insights From Dr Chemaly: The Role of NPs and PAs in Managing Patients During Prophylaxis and Their Role in Patient and Caregiver Education

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