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

Hannah Kaminski (1, 2) , Nassim Kamar (3, 4) , Olivier Thaunat (5) , Nicolas Bouvier (6) , Sophie Caillard (7) , Isabelle Garrigue (8) , Dany Anglicheau (9) , Jean-Philippe Rérolle (10) , Yannick Le Meur (11, 12) , Antoine Durrbach (13) , Thomas Bachelet (14) , Hélène Savel (15) , Roxane Coueron (15) , Jonathan Visentin (2, 16) , Arnaud del Bello (3, 4) , Isabelle Pellegrin (2, 17) , Julie Déchanet-Merville (2) , Pierre Merville (1, 2) , Rodolphe Thiébaut (15, 18) , Lionel Couzi (1, 2)

1 Service de Néphrologie Transplantation, Dialyse et Aphérèse [CHU Bordeaux]
2 ImmunoConcept - Immunology from Concept and Experiments to Translation
3 Département de Néphrologie et Transplantation d'organes [CHU Toulouse]
4 CPTP - Centre de Physiopathologie Toulouse Purpan
5 Department of Nephrology, Transplantation and Clinic Immunology [Hospices civils de Lyon]
6 Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen]
7 Service de Néphrologie et Transplantation [Strasbourg]
8 Virology Laboratory, Bordeaux University Hospital, Bordeaux, France
9 Service Néphrologie et transplantation rénale Adultes [CHU Necker]
10 Service de Néphrologie, Dialyse, Transplantations [CHU Limoges]
11 LBAI - Lymphocytes B, Autoimmunité et Immunothérapies
12 CHU - BREST - Nephrologie - CHRU Brest - Service de Nephrologie
13 Hôpital Henri Mondor - Service de néphrologie et transplantation
14 Department of Nephrology, Transplantation and Dialysis, Bordeaux, France
15 Pôle de Santé Publique - Service d’information Médicale [CHU de Bordeaux]
16 Service d'immunologie et d'immunogénétique [Bordeaux]
17 Laboratoire d'immunologie et d'immunogénétique [CHU Bordeaux]
18 SISTM - Statistics In System biology and Translational Medicine

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.

Mots clés: T cell biology; clinical research; clinical trial; immunosuppressant - mechanistic target of rapamycin: everolimus; infection and infectious agents - viral: Cytomegalovirus (CMV); kidney transplantation; nephrology; practice

Domaines: Immunologie

Hannah Kaminski, Nassim Kamar, Olivier Thaunat, Nicolas Bouvier, Sophie Caillard, et al.. Incidence of cytomegalovirus infection in seropositive kidney transplant recipients treated with everolimus: A randomized, open‐label, multicenter phase 4 trial. American Journal of Transplantation, 2022, ⟨10.1111/ajt.16946⟩. ⟨hal-03605036⟩