CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany.

Autor:	Bader P; Division for Stem Cell Transplantation, Immunology and Intensive Care, Department for Children and Adolescents, University Hospital, Goethe University, Frankfurt, Germany., Rossig C; Pediatric Hematology and Oncology, Muenster University Children's Hospital, Muenster, Germany., Hutter M; Division for Stem Cell Transplantation, Immunology and Intensive Care, Department for Children and Adolescents, University Hospital, Goethe University, Frankfurt, Germany., Ayuk FA; Department of Stem Cell Transplantation, Hamburg-Eppendorf University Medical Center, Hamburg, Germany., Baldus CD; Department of Internal Medicine II, Schleswig-Holstein University Hospital, Kiel, Germany., Bücklein VL; Department of Medicine III, University Hospital, Ludwig Maximilian University Munich, Munich, Germany., Bonig H; Goethe University Institute for Transfusion Medicine and lmmunohematology, Translational Development of Cellular Therapies, and German Red Cross Blood Service Baden-Württemberg-Hesse, Frankfurt, Germany., Cario G; Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany., Einsele H; Department of Medicine II, University Hospital of Wuerzburg, Wuerzburg, Germany., Holtick U; Department I of Internal Medicine, Medical Faculty and University Hospital Cologne, University of Cologne, Cologne, Germany., Koenecke C; Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany., Bakhtiar S; Division for Stem Cell Transplantation, Immunology and Intensive Care, Department for Children and Adolescents, University Hospital, Goethe University, Frankfurt, Germany., Künkele A; Department of Pediatric Oncology and Hematology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany., Meisel R; Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical lmmunology, Medical Faculty, Heinrich-Heine University, Duesseldorf, Germany., Müller F; Department of Internal Medicine 5, Haematology and Oncology, University Hospital of Erlangen, Friedrich Alexander University of Erlangen-Nürnberg (FAU), Erlangen, Germany., Müller I; Division of Pediatric, Stem Cell Transplantation and Immunology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany., Penack O; Department of Hematology, Oncology and Tumorimmunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany., Rettinger E; Division for Stem Cell Transplantation, Immunology and Intensive Care, Department for Children and Adolescents, University Hospital, Goethe University, Frankfurt, Germany., Sauer MG; Pediatric Hematology and Oncology, Medizinische Hochschule Hannover, Hannover, Germany., Schlegel PG; Department of Pediatric Hematology, Oncology, Stem Cell Transplantation, Wuerzburg University Children's Hospital, Wuerzburg, Germany., Soerensen J; Division for Stem Cell Transplantation, Immunology and Intensive Care, Department for Children and Adolescents, University Hospital, Goethe University, Frankfurt, Germany., von Stackelberg A; Department of Pediatric Oncology and Hematology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany., Strahm B; Faculty of Medicine, Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, University of Freiburg, Freiburg, Germany., Hauer J; Department of Pediatrics, Pediatric Hematology and Oncology, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.; Department of Pediatrics, Children's Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, Munich, Germany., Feuchtinger T; Department Pediatric Hematology, Oncology and Stem Cell Transplantation, Dr. von Hauner Children's Hospital, Ludwig Maximilian University Munich, Munich, Germany., Jarisch A; Division for Stem Cell Transplantation, Immunology and Intensive Care, Department for Children and Adolescents, University Hospital, Goethe University, Frankfurt, Germany.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2023 Jun 13; Vol. 7 (11), pp. 2436-2448.
DOI:	10.1182/bloodadvances.2022008981
Abstrakt:	Patients with precursor B-cell acute lymphoblastic leukemia (pB-ALL) who have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), have relapsed more than once, or are resistant upfront have a dismal prognosis. CD19-targeted chimeric antigen receptor (CAR) T cells have evolved as potent immune therapies. Tisagenlecleucel (Tisa-cel) is a commercially available autologous CD19-directed CAR T-cell product. We performed a retrospective study inviting all CAR T-cell centers in Germany to participate. Eighty-one patients with pB-ALL were included. Twenty-eight days after CAR T-cell infusion, 71 patients (87.7%) were in complete response, and 8 (9.9%) were in nonremission. At 2 years, the probabilities of event-free survival (pEFS), relapse-free survival (pRFS), and overall survival (pOS) were 45.3%, 51.7%, and 53.2%, respectively. pEFS was not different in patients without (n = 16, 55.0%) vs with prior allo-HSCT (n = 65, 43.4%). In patients treated after allo-HSCT, the time to relapse after allo-HSCT was a strong predictor of outcome. Patients relapsing within 6 months of allo-HSCT had a disappointing pEFS of 18.4% (pOS = 16.0%); the pEFS for those relapsing later was 55.5% (pOS = 74.8%). Our study provides real-world experience in pediatric, adolescent, and young adult patients with ALL treated with Tisa-cel, where most patients were treated after having relapsed after allo-HSCT. A total of 45.3% were rescued with a single dose of Tisa-cel. Our novel finding that patients with ALL after allo-HSCT had by far a better pEFS if relapse occurred beyond 6 months might be helpful in clinical decision-making and motivates studies to uncover the reasons. (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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