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
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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. / Gerbitz, Armin; Gary, Regina; Aigner, Michael; Moosmann, Andreas; Kremer, Anita; Schmid, Christoph; Hirschbuehl, Klaus; Wagner, Eva; Hauptrock, Beate; Teschner, Daniel; Roesler, Wolf; Spriewald, Bernd; Tischer, Johanna; Moi, Stephanie; Balzer, Heidi; Schaffer, Stefanie; Bausenwein, Judith; Wagner, Anja; Schmidt, Franziska; Brestrich, Jens; Ullrich, Barbara; Maas, Stefanie; Herold, Susanne; Strobel, Julian; Zimmermann, Robert; Weisbach, Volker; Hansmann, Leo; Lammoglia-Cobo, Fernanda; Remberger, Mats; Stelljes, Matthias; Ayuk, Francis; Zeiser, Robert; Mackensen, Andreas.
In: FRONT IMMUNOL, Vol. 14, 2023, p. 1251593.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -