Prevention of CMV/EBV reactivation by double-specific T cells in patients after allogeneic stem cell transplantation: results from the randomized phase I/IIa MULTIVIR-01 study

TY - JOUR

T1 - Prevention of CMV/EBV reactivation by double-specific T cells in patients after allogeneic stem cell transplantation: results from the randomized phase I/IIa MULTIVIR-01 study

AU - Gerbitz, Armin

AU - Gary, Regina

AU - Aigner, Michael

AU - Moosmann, Andreas

AU - Kremer, Anita

AU - Schmid, Christoph

AU - Hirschbuehl, Klaus

AU - Wagner, Eva

AU - Hauptrock, Beate

AU - Teschner, Daniel

AU - Roesler, Wolf

AU - Spriewald, Bernd

AU - Tischer, Johanna

AU - Moi, Stephanie

AU - Balzer, Heidi

AU - Schaffer, Stefanie

AU - Bausenwein, Judith

AU - Wagner, Anja

AU - Schmidt, Franziska

AU - Brestrich, Jens

AU - Ullrich, Barbara

AU - Maas, Stefanie

AU - Herold, Susanne

AU - Strobel, Julian

AU - Zimmermann, Robert

AU - Weisbach, Volker

AU - Hansmann, Leo

AU - Lammoglia-Cobo, Fernanda

AU - Remberger, Mats

AU - Stelljes, Matthias

AU - Ayuk, Francis

AU - Zeiser, Robert

AU - Mackensen, Andreas

N1 - Copyright © 2023 Gerbitz, Gary, Aigner, Moosmann, Kremer, Schmid, Hirschbuehl, Wagner, Hauptrock, Teschner, Roesler, Spriewald, Tischer, Moi, Balzer, Schaffer, Bausenwein, Wagner, Schmidt, Brestrich, Ullrich, Maas, Herold, Strobel, Zimmermann, Weisbach, Hansmann, Lammoglia-Cobo, Remberger, Stelljes, Ayuk, Zeiser and Mackensen.

PY - 2023

Y1 - 2023

N2 - INTRODUCTION: Allogeneic stem cell transplantation is used to cure hematologic malignancies or deficiencies of the hematopoietic system. It is associated with severe immunodeficiency of the host early after transplant and therefore early reactivation of latent herpesviruses such as CMV and EBV within the first 100 days are frequent. Small studies and case series indicated that application of herpes virus specific T cells can control and prevent disease in this patient population.METHODS: We report the results of a randomized controlled multi centre phase I/IIa study (MULTIVIR-01) using a newly developed T cell product with specificity for CMV and EBV derived from the allogeneic stem cell grafts used for transplantation. The study aimed at prevention and preemptive treatment of both viruses in patients after allogeneic stem cell transplantation targeting first infusion on day +30. Primary endpoints were acute transfusion reaction and acute-graft versus-host-disease after infusion of activated T cells.RESULTS: Thirty-three patients were screened and 9 patients were treated with a total of 25 doses of the T cell product. We show that central manufacturing can be achieved successfully under study conditions and the product can be applied without major side effects. Overall survival, transplant related mortality, cumulative incidence of graft versus host disease and number of severe adverse events were not different between treatment and control groups. Expansion of CMV/EBV specific T cells was observed in a fraction of patients, but overall there was no difference in virus reactivation.DISCUSSION: Our study results indicate peptide stimulated epitope specific T cells derived from stem cell grafts can be administered safely for prevention and preemptive treatment of reactivation without evidence for induction of acute graft versus host disease.CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov, identifier NCT02227641.

AB - INTRODUCTION: Allogeneic stem cell transplantation is used to cure hematologic malignancies or deficiencies of the hematopoietic system. It is associated with severe immunodeficiency of the host early after transplant and therefore early reactivation of latent herpesviruses such as CMV and EBV within the first 100 days are frequent. Small studies and case series indicated that application of herpes virus specific T cells can control and prevent disease in this patient population.METHODS: We report the results of a randomized controlled multi centre phase I/IIa study (MULTIVIR-01) using a newly developed T cell product with specificity for CMV and EBV derived from the allogeneic stem cell grafts used for transplantation. The study aimed at prevention and preemptive treatment of both viruses in patients after allogeneic stem cell transplantation targeting first infusion on day +30. Primary endpoints were acute transfusion reaction and acute-graft versus-host-disease after infusion of activated T cells.RESULTS: Thirty-three patients were screened and 9 patients were treated with a total of 25 doses of the T cell product. We show that central manufacturing can be achieved successfully under study conditions and the product can be applied without major side effects. Overall survival, transplant related mortality, cumulative incidence of graft versus host disease and number of severe adverse events were not different between treatment and control groups. Expansion of CMV/EBV specific T cells was observed in a fraction of patients, but overall there was no difference in virus reactivation.DISCUSSION: Our study results indicate peptide stimulated epitope specific T cells derived from stem cell grafts can be administered safely for prevention and preemptive treatment of reactivation without evidence for induction of acute graft versus host disease.CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov, identifier NCT02227641.

U2 - 10.3389/fimmu.2023.1251593

DO - 10.3389/fimmu.2023.1251593

M3 - SCORING: Journal article

C2 - 37965339

VL - 14

SP - 1251593

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

ER -