Hematopoietic Stem Cell Transplant: Infection Control - Episode 11

Considerations for Utilizing Letermovir in Practice


Roy Chemaly, MD: Letermovir has now been approved. We have changed our standard of care at my institution, and we’re going to start using letermovir for prophylaxis in all allogeneic stem cell transplant recipients who are recipient-positive for cytomegalovirus, to try to prevent this infection from the start. We’re going to start before engraftment, because data showed that letermovir had no impact on engraftment when you compared it to placebo. There was no real toxicity—mainly myelotoxicity or nephrotoxicity or even liver toxicity—when you compared it to placebo. So, it was safe enough to be used before engraftment. We’re going to start at day 7 and continue up to day 100, which is the highest-risk period. This is what our center is going to start doing in the near future, based on the encouraging data from the phase 3 trial that was recently published in the New England Journal of Medicine.

Letermovir should be started before engraftment. The reason is, we sometimes see early reactivation of CMV around the pre-engraftment period—that would be around day 9 or day 10. That’s why we made the decision at our institution to start at day 7. This way, we’ll cover all of the cases of CMV reactivation. You don’t want to have patients who already have reactivation. They won’t be eligible for a prophylactic regimen at that time. So, we have decided to start it early on, before engraftment, and continue it up to day 100.

Based on my involvement in the 2 clinical trials, the phase 2 and phase 3 trials, for letermovir, I feel confident that this is going to be a safe drug. We didn’t really see any kinds of signals for safety or toxicity with this drug. There were probably more patients on letermovir who had a little bit more nausea or vomiting when you compared it to placebo. Numerically, there was a higher number of patients with tachycardia, and some with atrial fibrillation. But, the events were mild to moderate in intensity. So, I feel confident that it’s going to be a safe drug for prophylaxis. We’re not going to have much of an issue, when you look at side effects.

What you need to be aware of, mainly, are the drug—drug interactions. There is a long list of drug–drug interactions. So, we have to monitor for this impact, or these kinds of interactions, as we go. When we put patients on prophylaxis with letermovir, we may have to check levels of immunosuppression with things like tacrolimus or cyclosporine, as well as antifungal therapy—mainly with voriconazole. So, we may have to be a little bit more vigilant, and should look for any kinds of adverse events that may be related to drug–drug interactions.

We’re going to learn more and more, as soon as we start using it. But, it’s something that we need to keep in mind. At least in our group, at our institution, I feel very confident that we have a very strong clinical pharmacist on our team. Our PharmDs are very helpful in tracking things and warning us about making adjustments, if need be, for these drug—drug interactions.

Transcript Edited for Clarity