Real-world effectiveness and safety of maribavir in solid organ transplant recipients with refractory/resistant cytomegalovirus or intolerance to anti-cytomegalovirus drugs: Interim results from the ARISE study

Introduction: The ARISE Study is assessing the use, effectiveness and safety of maribavir for the treatment of post-transplant cytomegalovirus (CMV) infection/disease in routine practice.
Methods: The ARISE Study is a real-world, retrospective cohort study evaluating maribavir use in adult transplant recipients with refractory/resistant (RR) CMV or intolerance (I) to anti-CMV agents in 10 European countries. Primary outcome is CMV clearance at maribavir discontinuation (last negative CMV PCR before maribavir discontinuation). Secondary outcomes include safety and healthcare resource utilization (HRU). We report interim data from solid organ transplant (SOT) recipients.
Results: The analysis included 124 SOT recipients (RR, n=99; I, n=25) with median (Q1–Q3) observation time of 22 (14–33) months. Mean (SD) age at transplant was 57 (13) years, 59% were male; 59% received kidney, 21% lung, and 15% heart transplants. Overall, 47 patients experienced ≥1 CMV episode before the index CMV episode (first maribavir-treated episode). The index episode was symptomatic in 54/98 (55%) RR and 11/25 (44%) I patients. In patients with available viral load (N=79), CMV clearance at maribavir discontinuation was achieved by 39/63 (62% [95% CI: 49–74]) RR and 14/16 (88% [62–98]) I patients. Kaplan-Meier (KM) estimates for achieving CMV clearance 56 days after maribavir initiation were 0.35 (95% CI: 0.25–0.48) and 0.80 (95% CI: 0.57–0.95) in the RR and I groups, respectively (Figure). During the index CMV episode maribavir monotherapy was the first treatment agent in 35/124 (28%) patients and second in 66/124 (53%). The median (Q1–Q3) duration of maribavir treatment courses (RR, n=114; I, n=25) was 57 (42–83) and 56 (44–57) days in RR and I patients, respectively, with 81/134 (60%) treatment course discontinuations due to CMV episode resolution. Maribavir was initiated at home in 84/118 (71%) and 11/25 (44%) treatment courses in RR and I patients, respectively. In 89 patients whose index episode ended (regardless of clearance confirmation), KM estimates of recurrence at day 56 post maribavir discontinuation were 0.39 (0.52–0.28) and 0.27 (0.51–0.13) in the RR and I groups. Adverse events and HRU are shown in the Table. Overall, 20 (21%) patients in the RR group died; cause of death was reported as “other”, transplant-related, and CMV-related in 53%, 32% and 15% of patients, respectively. Two (8%) patients in the I group died, cause of death was reported as “other”.
Conclusions: The data support real-world effectiveness and safety of maribavir in adult SOT recipients with RR and I CMV. The observed CMV clearance rates, and lower incidence of myelosuppression and hospitalizations after than prior to maribavir initiation, align with results from SOLSTICE. All-cause mortality was mostly attributed to non-CMV related causes, and rates were consistent with lower range estimates in the literature.