Association Between Cytomegalovirus Viremia Clearance and Post-Solid Organ Transplant Mortality in Patients With Refractory Cytomegalovirus Infection: SOLSTICE Post Hoc Analysis.
Kamar, N., et al.Transpl Int. 2025 Nov 26;38:15331.
Aims
To assess whether CMV viremia clearance at Week 8 is associated with all-cause mortality by Week 20 in solid organ transplant recipients with refractory CMV infection.
Interventions
This is a post hoc analysis of the SOLSTICE phase 3 trial, in which patients were randomised to maribavir 400 mg BID vs investigator-assigned therapy (ganciclovir/valganciclovir, foscarnet, or cidofovir) for 8 weeks, with 12 weeks follow-up. It re-stratifies patients from the SOLSTICE trial by virologic response at Week 8. Responders deemed those who achieved CMV DNA below LLOQ (137 IU/mL) in 2 consecutive samples ≥5 days apart at Week 8. Nonresponders were those patients who did not achieve clearance at Week 8 or needed maribavir rescue/alternative therapy before Week 8.
Participants
The 211 recipients from SOLSTICE included in this analysis: 97 responders and 114 nonresponders. The majority of recipients were D+/R− CMV serostatus (85.6% responders; 81.6% nonresponders).
Outcomes
All-cause mortality at Week 20, compared between responders vs nonresponders using Kaplan–Meier/log-rank.
Follow-up
20 weeks
CET Conclusions
This post-hoc analysis finds that in refractory CMV after transplant, failure to clear viremia by Week 8 is associated with a higher risk for short-term mortality compared to those who responded to treatment. At week 20 mortality was significantly higher in nonresponders with 10 deaths (3 in IAT nonresponders; 7 in maribavir nonresponders) compared with the 0 deaths in the responding group (log-rank p = 0.0024). Nonresponse was skewed more towards heart/lung recipients with an association for failing to achieve clearance (p=0.017). This is a post-hoc analysis of a trial in which mortality was not the primary endpoint, so inherently is limited, one can only infer that viremia clearance may be a marker of overall illness severity/immune competence rather than a causal factor in mortality. Combined with this, the event rate is small, with only 10 deaths, which limits multivariable modelling and precision in a post-hoc analysis of a complex patient group. Despite the limitations, clinically, the message is still useful. Virologic nonresponse after 8 weeks is a worrying feature, their findings support aggressive reassessment of antiviral strategy and heightened surveillance for complications and competing risks, which from their cohort appears to be thromboembolic events as well as CMV induced respiratory failure.
Trial registration
ClinicalTrials.gov - NCT02931539