Max S Topp1, Nicola Gökbuget2, Gerhard Zugmaier2, Petra Klappers2, Matthias Stelljes2, Svenja Neumann2, Andreas Viardot2, Reinhard Marks2, Helmut Diedrich2, Christoph Faul2, Albrecht Reichle2, Heinz-August Horst2, Monika Brüggemann2, Dorothea Wessiepe2, Chris Holland2, Shilpa Alekar2, Noemi Mergen2, Hermann Einsele2, Dieter Hoelzer2, Ralf C Bargou2. 1. Max S. Topp, Hermann Einsele, and Ralf C. Bargou, Universitätsklinikum Würzburg, Würzburg; Nicola Gökbuget, Goethe University; Dieter Hoelzer, Onkologikum, Frankfurt; Gerhard Zugmaier, Petra Klappers, and Noemi Mergen, Amgen Research; Dorothea Wessiepe, Metronomia, Munich; Matthias Stelljes, University of Münster, Münster; Svenja Neumann, Heinz-August Horst, and Monika Brüggemann, University Schleswig Holstein, City Hospital, Kiel; Andreas Viardot, University of Ulm, Ulm; Reinhard Marks, Universitätsklinikum Freiburg, Freiburg; Helmut Diedrich, Medizinische Hochschule Hannover, Hannover; Christoph Faul, Universitätsklinikum Tübingen, Tübingen; Albrecht Reichle, Universitätsklinikum Regensburg, Regensburg, Germany; and Chris Holland and Shilpa Alekar, Amgen, Rockville, MD. topp_m@ukw.de. 2. Max S. Topp, Hermann Einsele, and Ralf C. Bargou, Universitätsklinikum Würzburg, Würzburg; Nicola Gökbuget, Goethe University; Dieter Hoelzer, Onkologikum, Frankfurt; Gerhard Zugmaier, Petra Klappers, and Noemi Mergen, Amgen Research; Dorothea Wessiepe, Metronomia, Munich; Matthias Stelljes, University of Münster, Münster; Svenja Neumann, Heinz-August Horst, and Monika Brüggemann, University Schleswig Holstein, City Hospital, Kiel; Andreas Viardot, University of Ulm, Ulm; Reinhard Marks, Universitätsklinikum Freiburg, Freiburg; Helmut Diedrich, Medizinische Hochschule Hannover, Hannover; Christoph Faul, Universitätsklinikum Tübingen, Tübingen; Albrecht Reichle, Universitätsklinikum Regensburg, Regensburg, Germany; and Chris Holland and Shilpa Alekar, Amgen, Rockville, MD.
Abstract
PURPOSE: Patients with relapsed or refractory acute lymphoblastic leukemia (ALL) have a dismal prognosis. CD19 is homogenously expressed in B-precursor ALL and can be targeted by the investigational bispecific T cell-engager antibody blinatumomab. A phase II trial was performed to determine clinical activity in this patient cohort. PATIENTS AND METHODS: Thirty-six patients with relapsed or refractory B-precursor ALL were treated with blinatumomab in cycles of 4-week continuous infusion followed by a 2-week treatment-free interval in a single-arm study with a dose-finding stage and an extension stage. The primary end point was complete remission (CR) or CR with partial hematologic recovery (CRh). Major secondary end points included minimal residual disease (MRD) response, rate of allogeneic hematopoietic stem-cell transplantation (HSCT) realization, relapse-free survival (RFS), overall survival (OS), and incidence of adverse events (AEs). RESULTS: Median age was 32 years (range, 18 to 77 years). Twenty-five patients (69%) achieved a CR or CRh, with 88% of the responders achieving an MRD response. Median OS was 9.8 months (95% CI, 8.5 to 14.9), and median RFS was 7.6 months (95% CI, 4.5 to 9.5). Thirteen responders (52%) underwent HSCT after achieving a CR or CRh. The most frequent AE during treatment was pyrexia (grade 1 or 2, 75%; grade 3, 6%). In six patients with nervous system or psychiatric disorder AEs and in two patients with cytokine release syndrome, treatment had to be interrupted or discontinued. These medical events were resolved clinically. CONCLUSION: The data support further investigation of blinatumomab for the treatment of adult patients with relapsed or refractory ALL in a larger confirmatory study.
PURPOSE:Patients with relapsed or refractory acute lymphoblastic leukemia (ALL) have a dismal prognosis. CD19 is homogenously expressed in B-precursor ALL and can be targeted by the investigational bispecific T cell-engager antibody blinatumomab. A phase II trial was performed to determine clinical activity in this patient cohort. PATIENTS AND METHODS: Thirty-six patients with relapsed or refractory B-precursor ALL were treated with blinatumomab in cycles of 4-week continuous infusion followed by a 2-week treatment-free interval in a single-arm study with a dose-finding stage and an extension stage. The primary end point was complete remission (CR) or CR with partial hematologic recovery (CRh). Major secondary end points included minimal residual disease (MRD) response, rate of allogeneic hematopoietic stem-cell transplantation (HSCT) realization, relapse-free survival (RFS), overall survival (OS), and incidence of adverse events (AEs). RESULTS: Median age was 32 years (range, 18 to 77 years). Twenty-five patients (69%) achieved a CR or CRh, with 88% of the responders achieving an MRD response. Median OS was 9.8 months (95% CI, 8.5 to 14.9), and median RFS was 7.6 months (95% CI, 4.5 to 9.5). Thirteen responders (52%) underwent HSCT after achieving a CR or CRh. The most frequent AE during treatment was pyrexia (grade 1 or 2, 75%; grade 3, 6%). In six patients with nervous system or psychiatric disorder AEs and in two patients with cytokine release syndrome, treatment had to be interrupted or discontinued. These medical events were resolved clinically. CONCLUSION: The data support further investigation of blinatumomab for the treatment of adult patients with relapsed or refractory ALL in a larger confirmatory study.
Authors: U Duffner; A Abdel-Mageed; J Younge; C Tornga; K Scott; J Staddon; K Elliott; J Stumph; P Kidd Journal: Leukemia Date: 2016-02-09 Impact factor: 11.528
Authors: Katarzyna C Pituch; Markella Zannikou; Liliana Ilut; Ting Xiao; Michael Chastkofsky; Madina Sukhanova; Nicola Bertolino; Daniele Procissi; Christina Amidei; Craig M Horbinski; Karen S Aboody; C David James; Maciej S Lesniak; Irina V Balyasnikova Journal: Proc Natl Acad Sci U S A Date: 2021-03-02 Impact factor: 11.205
Authors: Marco Ruella; David M Barrett; Saad S Kenderian; Olga Shestova; Ted J Hofmann; Jessica Perazzelli; Michael Klichinsky; Vania Aikawa; Farzana Nazimuddin; Miroslaw Kozlowski; John Scholler; Simon F Lacey; Jan J Melenhorst; Jennifer J D Morrissette; David A Christian; Christopher A Hunter; Michael Kalos; David L Porter; Carl H June; Stephan A Grupp; Saar Gill Journal: J Clin Invest Date: 2016-08-29 Impact factor: 14.808