Cytomegalovirus-specific cell-mediated immunity for prediction of post-prophylaxis CMV disease in a phase 3 trial of letermovir vs valganciclovir prophylaxis in donor CMV-seropositive recipient CMV-seronegative kidney transplant recipients

Background QuantiFERON-CMV (QFT-CMV) is a standardized assay for the evaluation of cytomegalovirus-specific cell-mediated immunity (CMV-CMI). Objectives of this study were to assess the evolution of CMV-CMI post-transplant and the clinical utility of QFT-CMV for prediction of post-prophylaxis CMV disease in CMV-seronegative recipients of CMV-seropositive donor kidneys (D+R− KTRs). Methods 601 adult CMV D+R− KTRs received letermovir or valganciclovir prophylaxis for 28-weeks in a phase 3, double-blind, multicenter trial. QFT-CMV was performed at a central laboratory by masked personnel at transplant, 12, 28, and 52-weeks post-transplant. Investigators assessed CMV disease through week 52. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) at week 28 were used to evaluate clinical utility of QFT-CMV. Results Positive QFT-CMV results (pooled) were detected: baseline-1.2%, week 12-2.6%, week 28-7.7%, and week 52-28.9%. The distribution of positive results with letermovir and valganciclovir was comparable, except at week 28 (letermovir 2.2%, valganciclovir 12.8%). Post-prophylaxis CMV disease by week 52 occurred in 18.3% (84/460) of evaluable participants: 12.5% (4/32) of participants with a positive, 17.5% (66/377) with a negative, and 27.5% (14/51) with an indeterminate result at week 28 (p=not significant for all comparisons). QFT-CMV sensitivity, specificity, PPV, and NPV were 8.3%, 94.3%, 87.5%, and 17.5%, and were similar when pooling indeterminate and negative results and within letermovir and valganciclovir study arms. Conclusions Among adult CMV high-risk D+R− KTRs who received prophylaxis, CMV-CMI by QFT-CMV increased over time. The result at the end of prophylaxis had limited clinical utility for identifying the risk for subsequent CMV disease.