Abstract
BACKGROUND: Ruxolitinib (RUX) suppresses antiviral immunity in patients with hematologic diseases. For steroid-refractory acute graft-versus-host disease (aGVHD), studies have yielded conflicting results regarding whether RUX treatment increases the risk of Epstein-Barr virus (EBV) infection. However, in newly diagnosed aGVHD, the use of RUX raises concerns about the potential risk of EBV infection. This study aimed to evaluate the incidence of EBV reactivation and EBV-related posttransplant lymphoproliferative disease (EBV-PTLD) in patients receiving a regimen of 5 mg/day RUX combined with 1 mg·kg(-1)·d(-1) methylprednisolone as first-line therapy for aGVHD. METHOD: In this retrospective cohort study, allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients were consecutively screened at the Chinese PLA General Hospital. Patients who developed grade II-IV aGVHD were retrospectively categorized on the basis of first-line treatment. The RUX plus steroid (RUX-steroid) group (5 mg/day RUX + 1 mg·kg(-1)·d(-1) methylprednisolone) included patients who received this dose in a phase 2 dose-escalation study of RUX, the intervention arm of a phase 3 trial evaluating this regimen as first-line therapy for aGVHD, and patients who were deemed unsuitable for high-dose steroids owing to active infections. The steroid regimen group (2 mg·kg(-1)·d(-1) methylprednisolone) included patients treated in routine clinical practice and those in the control arm of the same phase 3 trial. EBV reactivation, EBV-PTLD incidence, and other transplantation outcomes were assessed. T-cell reconstitution was also analyzed at day 100 post-transplant. RESULTS: A total of 487 patients treated between January 2018 and December 2023 were included in this study, with a median follow-up of 26.6 months (range, 2.8-69.9). Among these patients, 105 received RUX (5 mg/day) plus methylprednisolone (1 mg·kg(-1)·d(-1)) as a first-line treatment for grade II-IV aGVHD and were categorized into the RUX-steroid group. Moreover, 115 patients who received methylprednisolone alone (2 mg·kg(-1)·d(-1)) formed the steroid group. The median duration of RUX exposure was 177 days (range, 17-447 days). The cumulative incidence of EBV reactivation within 180 days was significantly greater in the RUX-steroid group (82.9%) than that in the steroid group (70.2%) (hazard ratio [HR]: 1.43, 95% CI: 1.03-1.97; p = 0.03). The cumulative incidence of PTLD was comparable between the RUX-steroid group (5.0%) and the steroid group (4.5%) (HR: 1.12, 95% CI: 0.33-3.83; p = 0.86). Multivariate analysis revealed that the use of a matched-sibling donor (MSD) was significantly associated with a decreased risk of both EBV reactivation (p < 0.001) and EBV-PTLD (p = 0.034). The 2-year nonrelapse mortality (NRM) was 14.9% in the RUX-steroid group, comparable to 13.7% in the steroid group (HR: 1.01, 95% CI: 0.50-2.03; p = 0.98). CONCLUSION: RUX was associated with an increased risk of EBV reactivation in patients after allo-HSCT but not with PTLD. Regular monitoring of the EBV viral load to enable timely intervention remains essential in these patients.