CMV resistance to maribavir rare at baseline but may emerge
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Key takeaways:
- CMV resistance to maribavir was less common than resistance to other treatments assigned after transplant.
- However, resistance may develop after several weeks of treatment.
Among transplant recipients treated for cytomegalovirus, resistance to maribavir was less common than resistance to investigator-assigned standard therapy, at baseline and post-treatment, researchers reported.
However, data from more than 230 patients receiving maribavir after undergoing a solid organ or hematopoietic stem cell transplant did see strong evidence of emerging drug resistance to maribavir while on treatment.
“For a long time, the only approved systemic antiviral drugs for treatment of human cytomegalovirus (CMV) infections consisted of ganciclovir, its prodrug valganciclovir, foscarnet and cidofovir, all targeting the viral DNA polymerase. Recently, maribavir was approved for treatment of CMV infections refractory (with or without resistance) to standard therapy,” Sunwen Chou, MD, professor emeritus of medicine in the division of infectious diseases at Oregon Health and Science University, and colleagues wrote.
“Because resistance to the newer CMV antivirals letermovir (approved for use as prophylaxis) and maribavir appears to be readily selected in vitro, their incidence of drug resistance in clinical use requires attention,” the researchers wrote.
As part of the previously published phase 3 SOLSTICE trial, Chou and colleagues performed a drug resistance analysis of a randomized trial including 234 transplant recipients receiving maribavir and 116 receiving investigator-assigned standard therapy (IAT), during which time, 56% of those receiving maribavir and 24% of those receiving IAT cleared CMV DNA at week 8. They were referred to as treatment responders moving forward. According to the study, baseline and post-treatment plasma samples were then tested for mutations showing drug resistance in viral genes UL97, UL54 and UL27.
The study revealed that, at baseline, genotypic testing showed resistance to ganciclovir, foscarnet or cidofovir in 56% of patients receiving maribavir and 68% receiving IAT, including nine newly phenotyped mutations. Among the cases of resistance, 63% were among maribavir treatment responders and 21% were among IAT treatment responders. The maribavir resistance mutations detected at baseline were UL27 L193F and UL97 F342Y.
Additionally, the study showed that post-treatment-emergent maribavir resistance mutations were detected in 60 (26%) of those treated with maribavir, including 48% nonresponders and 86% of nonresponders who initially cleared but then rebounded while on maribavir. According to the study, the most common resistance mutations were UL97 T409M, H411Y and C480F.
“Viral mutations may appear after several weeks of maribavir treatment and their detection requires a wider scope of UL97 genotypic testing than was prevalent in the past. This testing may be especially indicated where a rebound in viral load occurs while on maribavir therapy,” the authors wrote. “Future research includes surveillance for other UL97 or UL27 mutations that may affect maribavir susceptibility.”
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