S291: long-term safety and efficacy of cmv/ebv-specific t cells for cmv and ebv co-reactivation after haploidentical stem cell transplantation

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Viral infections occur frequently in a significant proportion of recipients after haploidentical stem cell transplantation (haplo-SCT) and can cause potentially life-threatening complication. Concurrent and sequential multivirus infections, especially cytomegalovirus (CMV) and Epstein-Barr virus (EBV), are common and lead worse clinical outcomes. Standard antiviral therapies are unsatisfactory owing to substantial side effects, limited efficacy, and risk of developing drug resistance. Adoptive therapy with multivirus-specific T-cells has shown promise in preventing or treating viral infections in clinical trials. However, the safety and durability were evaulated in patients with single virus reactivations. For patients with co-reactivation of multivirus infections, the role of multivirus-specific T cells have yet to be established. Aims: We aimed to investigate the long-term safety and efficacy of donor-derived multi-epitope CMV/EBV-specific T cells (VSTs) for CMV and EBV co-reactivation after haplo-SCT. Methods: We analyzed 93 adult patients who received VSTs therapy for CMV and EBV co-infection after haplo-SCT at our center from 2015 to 2019. Of the 93 patients enrolled, 71 patients were with refractory CMV infection, 12 patients with CMV disease, and 26 patients with EBV-associated posttransplant lymphoproliferative disease (PTLD). Thirty-one patients had uncrolled CMV and EBV co-infections at time of VSTs infusion. The cumulative positive time for CMV and EBV viremia was 21 (range, 1-92) days and 14 (range, 3-35) days respectively before VSTs infusion. Complete response (CR) was defined as both CMV and EBV viral load decrease to below the limits of assay detection in two consecutive tests coupled, with the resolution of clinical signs and symptoms. Results: Seventy-five patients had a single infusion, 14 patients had 2 infusions and 4 patients had 3 infusions. No serious infusion-related adverse events, including cytokine release syndrome and grade 3-4 acute graft-versus-host disease, were observed. The median time of CMV and EBV persistence was 8 (0-88) days and 3 (0-207) days respectively post VSTs infusion. All of the 93 patients responded to VSTs, with a 4-week cumulative CR rate of 92.5% (95% CI, 87.2%-97.8%). Of the 86 patients who achieved CR, 32 responders did not exhibit CMV or EBV reactivation for the duration of follow-up, 38 responders develpoed a transient controllable viral recurrence. At 2 years post-transplant, overall survival was 71.5% (95% CI, 62.3%-80.7%). Summary/Conclusion: This study represents the largest study conducted to date on the clinical utility of multivirus-specific T-cells, and is the first one to evaluate the antiviral efficacy of VSTs for co-reactivation of multivirus infections. Our data showed that adoptive therapy with VSTs is a safe and effective treatment for CMV and EBV co-infections after haplo-SCT. Keywords: Cellular therapy, Hematopoietic cell transplantation, EBV, CMV infection