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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

Activity

Progress
1
Course Completed

Managing Side Effects and Toxicity of Antivirals in PET

Myelosuppression is the major toxicity of ganciclovir and valganciclovir, which impacts efficacy and increases risk for secondary infections. Neutropenia with ganciclovir usually develops during the first 2 weeks of treatment but can develop at any time with ganciclovir or valganciclovir. Neither drug is recommended for patients with existing absolute neutrophil counts (ANC) <500 cells/µL, hemoglobin <8 g/dL, or platelets <25,000 cells/µL.14,15 In clinical trials with allo-HCT patients who received ganciclovir, ANC <500 cells/µL occurred in 12% and a total of 41% had ANC <1000 cell/µL; a total of 51% had platelets <50,000 cells µL, including 31% with platelets <25,000 cells/µL.14 In clinical trials with valganciclovir for CMV retinitis, ANC <500 cells/µL occurred in 19% of patients.15

In a comparison of valganciclovir with ganciclovir for PET following HCT, no severe side effects were reported. Patients who received ganciclovir were more likely to require erythrocyte transfusion, but the difference was not significant.16 The most frequent nonhematologic side effects with valganciclovir include diarrhea, fever, fatigue, headache, insomnia, urinary tract infection/upper respiratory tract infection, and vomiting.15 Valganciclovir has the advantage of oral administration, whereas ganciclovir, foscarnet, and the others are IV drugs.7 

Foscarnet has also been used for PET and does not cause myelosuppression. The most concerning toxicity with foscarnet is nephrotoxicity and electrolytes imbalance, with 14% of patients experiencing severe renal impairment in clinical trials.17 The drug directly damages renal tubular cells. Toxicity usually develops within 2 weeks of induction, but can occur at any time, and patients must be monitored regularly while on treatment. Foscarnet should be avoided for patients with existing renal impairment.17,18 Another toxicity of special concern is electrolytes imbalances—principally in potassium and magnesium—that lowers seizure thresholds and requires regular monitoring. Hydration with normal saline or dextrose solution prior to or during infusion may reduce these risks; patients require close monitoring and rapid treatment to correct electrolytes imbalances should they occur.17,18 Other side effects that have been reported with foscarnet include QT prolongation, hypersensitivity reactions, and dizziness. Patients should have ECG and electrolyte measurement prior to starting treatment and at intervals on treatment.17

Valganciclovir and ganciclovir have boxed warnings for hematologic toxicity (including bone marrow failure), fertility impairment in males and females, and fetal toxicity.14,15 Foscarnet has boxed warnings for renal impairment and potential for seizures related to electrolyte imbalances.17

Maribavir is an oral drug that has demonstrated efficacy similar to valganciclovir in PET. It is associated with dysgeusia and some gastrointestinal toxicity. The most common gastrointestinal toxicity was dysgeusia, reported in from 15% to 82% of clinical trial participants. It has a very low rate of neutropenia and no significant nephrotoxicity or marrow toxicity.18,19 Maribavir is FDA approved for treatment of refractory CMV infection with or without genotypic resistance post-transplant.19

In contrast, cidofovir is a once-weekly IV drug associated with risk of nephrotoxicity and renal tubular damage that limit its utility for PET. It is more often reserved for treatment of resistant CMV infections.18 

Expert Insights From Dr Chemaly: Toxicities of Ganciclovir/Valganciclovir and Impact on Patient Outcomes of Neutropenia/Cytopenia and Dose Adjustment/Interruption

Which of these has demonstrated improved survival as CMV prophylaxis post–allo-HCT?

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