Incidence of cytomegalovirus infection in seropositive kidney transplant recipients treated with everolimus: A randomized, open-label, multicenter phase 4 trial

Abstract

Cytomegalovirus (CMV) persists as the most frequent opportunistic infection among solid organ transplant recipients. This multicenter trial aimed to test whether treatment with everolimus (EVR) could decrease the incidence of CMV DNAemia and disease. We randomized 186 CMV seropositive kidney transplant recipients in a 1:1 ratio to receive EVR or mycophenolic acid (MPA) in association with basiliximab, cyclosporin, and steroids and 87 in each group were analyzed. No universal prophylaxis was administered to either group. The composite primary endpoint was the presence of CMV DNAemia, CMV treatment, graft loss, death, and discontinuation of the study at 6 months posttransplant. In the modified intent‐to‐treat analysis, 42 (48.3%) and 70 (80.5%) patients in the EVR and MPA groups reached the primary endpoint (OR = 0.21, 95% CI: 0.11–0.43, p < .0001). Fewer patients of the EVR group received treatment for CMV (21.8% vs. 47.1%, p = .0007). EVR was discontinued in 31 (35.6%) patients. Among the 56 patients with ongoing EVR treatment, only 7.4% received treatment for CMV. In conclusion, EVR prevents CMV DNAemia requiring treatment in seropositive recipients as long as it is tolerated and maintained.

The case for the therapeutic use of mechanistic/mammalian target of rapamycin (mTOR) inhibitors in xenotransplantation

“…64 There is increasing evidence that mTOR-Is have anti-CMV properties. 23,[77][78][79] They have indirect anti-viral activity and reduce the rate of CMV infection in CMV-seropositive organ transplant recipients. 80 mTOR-Is inhibit proliferation of infected cells by activating specific signaling pathways.…”

“…There is increasing evidence that mTOR‐Is have anti‐CMV properties 23,77–79 . They have indirect anti‐viral activity and reduce the rate of CMV infection in CMV‐seropositive organ transplant recipients 80 .…”

Anti-CMV therapy, what next? A systematic review

“…A more recent Phase IV trial was conducted with 186 seropositive HCMV kidney recipients randomized (1:1) to receive EVR or MPA in combination with basiliximab, cyclosporine and steroids. In seropositive recipients, HCMV DNAemia is prevented by EVR treatment until it is no longer tolerated or stopped ( Kaminski et al, 2022a ). In addition, the same authors reported that the T-cell phenotype may offer a new biomarker for predicting post-transplant infection and classifying patients who should be eligible for EVR treatment ( Kaminski et al, 2022b ).…”

Slaying the “Troll of Transplantation”—new frontiers in cytomegalovirus management: A report from the CMV International Symposium 2023

“…Immunosuppressive therapy (IST) is vital post SOT and response to pre‐emptive antiviral therapies may vary depending on choice of IST 33 . A randomized, open‐label study in seropositive kidney transplant recipients demonstrated greater benefit with pre‐emptive therapy when ciclosporin‐treated patients were receiving a mammalian target of rapamycin (mTOR) inhibitor, such as everolimus, rather than mycophenolic acid ( p < .0001) 34 . A clear lower rate of CMV infection has also been demonstrated in randomized trials of everolimus in heart transplant recipients 35,36 .…”