Safety and efficacy of immunoguided prophylaxis for cytomegalovirus disease in low-risk lung transplant recipients in Spain: a multicentre, open-label, randomised, phase 3, noninferiority trial.

Summary

In a multicentre phase 3 randomized noninferiority trial (n=150), immunoguided CMV prophylaxis (3 months of valganciclovir followed by CMV-specific T‑cell–guided discontinuation) was noninferior to standard 6‑month prophylaxis for preventing CMV disease through 18 months (18.7% vs 16.0%; RD −0.03). The approach reduces antiviral exposure without compromising efficacy.

Key Findings

• Immunoguided prophylaxis was noninferior to standard prophylaxis for 18‑month CMV disease incidence (18.7% vs 16.0%; risk difference −0.03, 95% CI −0.15 to 0.06).
• The strategy inherently reduces valganciclovir exposure by halving universal prophylaxis duration (3 vs 6 months).
• Trial conducted across seven centers with randomized, open-label design and predefined noninferiority margin (7%).

Clinical Implications

Centers can consider adopting CMV cell-mediated immunity assays to tailor valganciclovir duration, potentially lowering drug toxicity (e.g., neutropenia) and costs while maintaining CMV control.

Limitations

• Open-label design may introduce performance bias
• Conducted in CMV-seropositive, lower-risk recipients; generalizability to higher-risk populations is uncertain

Future Directions

Cost-effectiveness analyses, validation across diverse risk strata and regions, and operational pathways for integrating CMV-specific T‑cell assays into routine post-transplant care.