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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

Roy F. Chemaly
Roy F. Chemaly, MD, MPH
CME/CE Information

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Managing Aspects of Prophylaxis With Letermovir

The most concerning aspect of treatment with letermovir is risk for clinically relevant drug–drug interactions. Letermovir is a substrate and inhibitor of several key pathways, including OATP 1B1/3, UGT1A1/3, and efflux transporters (eg, P-glycoprotein).21,30 Coadministration with drugs that are CYP3A substrates or are OATP1B1/3 substrates may increase concentration of those drugs. This affects a substantial number of other drugs in various ways; in transplantation, letermovir can reduce or increase the effects of immunosuppressant drugs and extended-spectrum azole drugs. Conversely, coadministration of letermovir with some drugs may reduce letermovir effect. The complete list of drug–drug interactions is extensive and should be reviewed before treatment planning.21,30

In a phase III trial, more patients receiving letermovir (71.0%) than placebo (41.2%) completed the trial regimen through Week 14. Similar percentages of patients experienced adverse events (any: 97.9% vs 100%, respectively), including nausea, which was the most frequent reason for discontinuation (26.5% vs 23.4%), diarrhea (26.0% vs 24.5%), vomiting (18.5% vs 13.5%), headache (13.9% vs 9.4%), and others.22 Another frequent side effect is peripheral edema, which was reported in 14% of patients receiving letermovir and 9.4% receiving placebo.30 Hematologic and renal toxicity occurred in similar percentages of patients treated with letermovir and placebo.22,30 Overall, 19% of patients in each group developed severe neutropenia (<500 cells/µL). Other outcomes with letermovir vs placebo, respectively, were hemoglobin <6.5 g/dL 2% vs 1%; platelets <25,000 cells/µL 27% vs 21%; and serum creatinine >2.5 mg/dL 2% vs 3%. Severity of adverse events was similar with letermovir or placebo, and similar percentages discontinued due to side effects (13% vs 12%).30 In long-term follow-up of patients who received letermovir, no additional toxicities have emerged. 

Currently recommended agents for treatment and prevention are summarized in Table 3.7,13,34,35 

Table 3. Drugs for Treatment/Prevention of CMV After Allo-HCT*7,13,34,35

Expert Insights From Dr Chemaly: Use of Letermovir in Clinical Practice and How We Manage Drug–drug Interactions and Toxicities

Which of these factors favors PET vs prophylaxis in patients undergoing allo-HST?

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