P-1196. Drug-Drug Interactions (DDIs) With Letermovir (LET) for Cytomegalovirus (CMV) Prophylaxis in Pediatric (Birth to < 18 years of age) Hematopoietic Cell Transplant (HCT) Recipients

Abstract Background HCT recipients receive multiple medications post-transplant, increasing the potential for DDIs. LET, a CMV terminase complex inhibitor approved for CMV prophylaxis in adult CMV-seropositive allogeneic HCT recipients, has the potential for DDIs with multiple medications commonly used in the HCT setting. As LET-associated DDIs have been well characterized in adults, the objective of this analysis was to evaluate known LET-associated DDIs in pediatric HCT recipients, including impact on patient safety, in a recently completed Phase 2 nonrandomized, multicenter, open-label study (NCT03940586) which evaluated LET prophylaxis in pediatric allo-HCT recipients. Methods Participants from birth to < 18 years of age were enrolled within 28 days post-HCT to receive LET through 14 weeks (∼100 days) post-HCT and followed through Week 48 post-HCT. Medications with potentially significant drug interactions (per the LET US label) administered concomitantly with LET were assessed in all study participants. Results A total of 63 enrolled participants received at least one dose of LET. Sixty-two (98.4%) participants received one or more concomitant medications with a potentially significant LET-associated DDI, and 50 (79.4%) participants received two or more LET-associated DDI medications. The most common concomitant medications with a LET-associated DDI were cyclosporin A (60.3% [38/63]), tacrolimus (41.3%), and voriconazole (39.7%). DDIs were reported as an adverse event (AE) in five (7.9%) participants: cyclosporin A increased (n=2), voriconazole decreased (n=2), and tacrolimus interaction (n=1). LET was discontinued in one participant due to decreased voriconazole levels. No AEs or deaths were reported due to these DDI events. Conclusion Concomitant administration of LET with medications with known potentially significant LET-associated DDIs was generally safe and well tolerated in pediatric HCT recipients. Disclosures Lara A. Danziger-Isakov, MD, MPH, Aicuris: clinical research contract, paid to institutio|Ansun BioPharma: clinical research contract, paid to institution|Astellas: Advisor/Consultant|Astellas: clinical research contract, paid to institutio|Merck: clinical research contract, paid to institutio|Pfizer: Grant/Research Support|Takeda: clinical research contract, paid to institutio Andreas H. Groll, MD, Amplyx: Advisor/Consultant|Astellas: Advisor/Consultant|Astellas: Speaker bureau|Basilea: Advisor/Consultant|Basilea: Speaker bureau|F2G: Advisor/Consultant|F2G: Speaker bureau|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Speaker bureau|Merck Sharp & Dohme LLC: Advisor/Consultant|Merck Sharp & Dohme LLC: Grant/Research Support|Merck Sharp & Dohme LLC: Speaker bureau|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Speaker bureau|Subsidiary of Merck & Co: Advisor/Consultant|Subsidiary of Merck & Co: Grant/Research Support|Subsidiary of Merck & Co: Speaker bureau Natasha Broyde, MS, Merck Sharp & Dohme LLC,: Current employee|Merck Sharp & Dohme LLC,: Stocks/Bonds (Public Company) Barbara A. Haber, MD, Merck & Co., Inc: Employee of Merck & Co., Inc Christopher L. Gilbert, n/a, Merck Sharp & Dohme LLC: Current employee|Merck Sharp & Dohme LLC: Stocks/Bonds (Public Company) Cyrus Badshah, MD, PhD, Merck Sharp & Dohme LLC: Current employee|Merck Sharp & Dohme LLC: Stocks/Bonds (Public Company)