518 - Real-World Adherence and Toxicity of Valganciclovir for Congenital Cytomegalovirus

Publication Number: 3499.518

Aanchal Wats, Yale School of Medicine, New Haven, CT, United States; Barbara Luiza R. Araujo, Yale School of Medicine, Department of Pediatrics, New Haven, CT, United States; Camila Aparicio Llorente, Yale School of Medicine, New Haven, CT, United States; Julia Moniz Ganem, Yale School of Medicine, New Haven, CT, United States; Isabela Oliva, Yale School of Medicine, New Haven, CT, United States; Carlos R. Oliveira, Yale School of Medicine, New Haven, CT, United States

Background: Cytomegalovirus (CMV) is the most common congenital infection worldwide, affecting 0.5%–0.7% of live births. Antiviral therapy can improve long-term hearing and neurodevelopmental outcomes in infants with moderate to severely symptomatic congenital CMV (cCMV) disease. However, the efficacy of antivirals like valganciclovir is often limited by drug toxicities, most notably neutropenia, which has a reported incidence of approximately 20% in clinical trials, often necessitating dose adjustments or treatment interruptions. Understanding real-world treatment adherence and the manageability of toxicity is essential to optimizing care.

Objective: To evaluate treatment completion and characterize the incidence, timing, and management of valganciclovir-associated toxicities in infants with cCMV.

Design/Methods: This retrospective observational study identified cCMV cases from January 1, 2013, to December 31, 2023, within a large healthcare system in Connecticut. Cases were identified using an EHR algorithm (laboratory results, ICD codes, and valganciclovir prescriptions) and validated by chart review. Treatment completion was defined as clinician-documented completion of the planned course. Toxicities were identified through laboratory and clinical documentation and independently adjudicated by two clinicians with consensus resolution. Extracted data included demographics, clinical features, laboratory results, treatment interruptions, and reasons for discontinuation.

Results: A total of 58 infants with cCMV were identified (54 confirmed; 4 probable), with antiviral therapy prescribed for 39 (67%) of them. Most treated infants (35/39; 90%) were moderately to severely symptomatic and were prescribed valganciclovir for six months. Treatment was completed by 31 of 39 (79%). Among the 8 infants (21%) who did not complete therapy, early disease-related death accounted for 2 (5%), parental discontinuation for 3 (8%), and toxicity-related discontinuation for 3 (8%). Treatment-related toxicity occurred in 13 of 39 treated infants (33%). Neutropenia was observed in 11 of 39 (28%), anemia in 3 of 39 (8%), transaminitis in 2 of 39 (5%), and emesis in 1 of 39 (3%). The onset of neutropenia peaked between weeks 4-6 of therapy, but initial occurrences were noted as early as week 2. Ten of the 13 infants with toxicity (77%) completed treatment after short interruptions or dose changes.

Conclusion(s): Despite frequent toxicity, most infants with cCMV completed the planned valganciclovir treatment course. The early onset of cytopenias supports close hematologic monitoring during treatment.