An Analysis of Cytomegalovirus-Specific Cell-Mediated Immunity in a Phase 3, Randomized, Placebo-Controlled Trial of Letermovir Prophylaxis in Cytomegalovirus-Seropositive Recipients of an Allogeneic Hematopoietic Cell Transplant.

Abstract

Cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) prevents CMV reactivation after hematopoietic cell transplant (HCT). Trends in CMV-CMI using the QuantiFERON-CMV assay and its clinical utility in a Phase 3 study were evaluated. Cytomegalovirus-seropositive allogeneic HCT recipients who received letermovir prophylaxis through ∼100 days post-HCT were randomized to receive letermovir or placebo through ∼200 days post-HCT. QuantiFERON-CMV was performed at 100 days, 200 days, and Week 48 post-HCT. QuantiFERON-CMV results after prophylaxis completion (∼100 and ∼200 days post-HCT in placebo and letermovir groups, respectively) were evaluated for predicting postprophylaxis clinically significant CMV infection (CS-CMVi) through Week 48 post-HCT. QuantiFERON-CMV assay positivity was similar at study entry between letermovir (n = 82) and placebo (n = 47) groups (30.5% vs 31.9%), higher for placebo group at 200 days post-HCT (48.8% vs 74.5%), and comparable between groups at Week 48 post-HCT (65.9% vs 74.5%). Postprophylaxis CS-CMVi occurred by Week 48 in 10.5% (6/57) of participants with a positive result versus 19.0% (8/42) with a negative result at 200 days post-HCT in the letermovir group and 10.3% (3/29) of participants with a positive result versus 20.7% (6/29) with a negative result at 100 days post-HCT in the placebo group. Assay sensitivity, specificity, positive predictive value, and negative predictive value were 60.0%, 57.1%, 89.5%, and 19.0% for tests at 200 days post-HCT (letermovir) and 53.1%, 66.7%, 89.7%, and 20.7% for tests at 100 days post-HCT (placebo). Positive QuantiFERON-CMV results increased after letermovir prophylaxis completion. Predictive utility of the QuantiFERON-CMV assay may be limited in the HCT setting.