Introduction: Cytomegalovirus (CMV), a common infection among solid organ transplant (SOT) recipients, can lead to a higher risk of mortality and morbidity in these patients. However, management of CMV infection can be limited by toxicities or intolerances with anti-CMV agents including ganciclovir, valganciclovir or foscarnet. This study aimed to describe treatment patterns, clinical outcomes, and healthcare resource utilization in SOT recipients with CMV infection and intolerance to anti-CMV agents based on real-world data.
Method: This multicenter, retrospective study included adult SOT recipients with CMV infection refractory or resistant to treatment, or with intolerance (RRI) to anti-CMV agents. Data were collected from 13 centers across Europe and USA between 2014 and 2021. This analysis focused on patients whose first CMV episode was considered intolerant to anti-CMV treatment; patients whose first CMV episode was considered resistant or refractory to anti-CMV treatment were excluded. Patients may have experienced previous non-RRI episodes and/or subsequent CMV episodes (including RRI) after their first intolerant episode. Treatment patterns, outcomes, and hospitalizations were analyzed using descriptive statistics.
Results: In total, 53 of 218 patients enrolled were intolerant to anti-CMV agents (median age: 56 years; 72% male). Median (Q1–Q3) time from SOT until first intolerance identification was 211 (128–265) days. Patients spent a median (Q1–Q3) of 21 (8–30) days on anti-CMV treatment before intolerance identification. At intolerance identification, and for all CMV episodes, valganciclovir was the most frequently used anti-CMV agent (81% and 87% respectively), followed by ganciclovir (13% and 32%; patients could receive ≥1 type of anti-CMV agent during a CMV episode). Of 51 patients with available data, 15 (29%) received ≥2 therapies for all CMV episodes. One or more anti-CMV therapy dose change was prescribed for 91% of patients, most commonly with valganciclovir (83%) or ganciclovir (35%). Reasons for dose changes with valganciclovir included CMV viremia resolution (55%), lower dose for maintenance (35%), and leukopenia (25%). Intolerance was most commonly due to myelosuppression or renal toxicity (Table). Death due to any cause was 28% (median follow-up 1295 days) and mortality at 1-year post-intolerance identification was 17%. Viremia clearance was achieved in 42 (79%) patients during their first intolerant CMV episode (Table). Seven (13%) patients experienced 1 CMV-related hospitalization, and ten (19%) patients experienced organ rejection.
Conclusion: These results highlight the high burden of intolerance to anti-CMV agents in SOT recipients with CMV infection. Alongside the risk of adverse outcomes, many patients fail to achieve viremia clearance and/or experience recurrence. There is a need for treatments with improved safety profiles that can achieve and maintain CMV clearance.