Safety and efficacy of glofitamab for relapsed/refractory large B-cell lymphoma in a multinational real-world study
Abstract: Glofitamab, a bispecific antibody targeting CD20 and CD3, is approved for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) after at least 2 prior treatment lines, but real-world data are scarce. In this retrospective, multicenter, multinational study, we evaluated the outcomes...
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Elsevier
2025-08-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952924007195 |
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| author | Evgenii Shumilov Rebecca Wurm-Kuczera Andrea Kerkhoff Meng Wang Thomas Melchardt Udo Holtick Ulrike Bacher Philipp Staber Paolo Mazzeo Corinna Leng David Böckle Alexander Hölscher Joseph Kauer Natalia Rotter Vladan Vucinic Jakob Rudzki David Nachbaur Veit Bücklein Ulf Schnetzke Isabelle Krämer Kai Wille Alexander Hasse Bastian von Tresckow Mathias Hänel Christian Koenecke Giuliano Filippini Velazquez Andreas Viardot Christoph Schmid Lorenz Thurner Dominik Wolf Marion Subklewe Martin Dreyling Peter Dreger Sascha Dietrich Ulrich Keller Ulrich Jäger Richard Greil Thomas Pabst Georg Lenz Björn Chapuy |
| author_facet | Evgenii Shumilov Rebecca Wurm-Kuczera Andrea Kerkhoff Meng Wang Thomas Melchardt Udo Holtick Ulrike Bacher Philipp Staber Paolo Mazzeo Corinna Leng David Böckle Alexander Hölscher Joseph Kauer Natalia Rotter Vladan Vucinic Jakob Rudzki David Nachbaur Veit Bücklein Ulf Schnetzke Isabelle Krämer Kai Wille Alexander Hasse Bastian von Tresckow Mathias Hänel Christian Koenecke Giuliano Filippini Velazquez Andreas Viardot Christoph Schmid Lorenz Thurner Dominik Wolf Marion Subklewe Martin Dreyling Peter Dreger Sascha Dietrich Ulrich Keller Ulrich Jäger Richard Greil Thomas Pabst Georg Lenz Björn Chapuy |
| author_sort | Evgenii Shumilov |
| collection | DOAJ |
| description | Abstract: Glofitamab, a bispecific antibody targeting CD20 and CD3, is approved for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) after at least 2 prior treatment lines, but real-world data are scarce. In this retrospective, multicenter, multinational study, we evaluated the outcomes of 70 patients with r/r DLBCL treated with glofitamab as part of the compassionate use patient program in Germany, Austria, and Switzerland. The median number of prior treatment lines was 4, with 71% of patients refractory to their last treatment. Cytokine release syndrome was observed in 40% of patients (grade 3-4 in 2%), immune effector cell–associated neurotoxicity syndrome in 10% (grade 3 in 1%), and infections in 31% (grade 5 in 3%). The overall response rate was 46%, with 27% achieving complete responses (CR) and 19% partial responses. The median progression-free survival (PFS) was 3.6 months, whereas the median overall survival was 5.7 months. Notably, 13 patients (19%) were in CR 6 months after initiating glofitamab and exhibited durable responses. Elevated lactate dehydrogenase is the most robust predictor of inferior outcome. Patients pretreated with bendamustine within 6 months prior to glofitamab initiation exhibited significantly reduced PFS, suggesting that bendamustine may impair T-cell fitness and hence glofitamab efficacy. In summary, glofitamab demonstrates promising efficacy and a manageable safety profile in heavily pretreated patients with r/r DLBCL in a real-world scenario and the optimal sequence of treatments should use T-cell–depleting agents before glofitamab with caution. |
| format | Article |
| id | doaj-art-2b95095312c442e79d5c2a1298b8a8bf |
| institution | Kabale University |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-2b95095312c442e79d5c2a1298b8a8bf2025-08-20T03:31:37ZengElsevierBlood Advances2473-95292025-08-019153865387710.1182/bloodadvances.2024014903Safety and efficacy of glofitamab for relapsed/refractory large B-cell lymphoma in a multinational real-world studyEvgenii Shumilov0Rebecca Wurm-Kuczera1Andrea Kerkhoff2Meng Wang3Thomas Melchardt4Udo Holtick5Ulrike Bacher6Philipp Staber7Paolo Mazzeo8Corinna Leng9David Böckle10Alexander Hölscher11Joseph Kauer12Natalia Rotter13Vladan Vucinic14Jakob Rudzki15David Nachbaur16Veit Bücklein17Ulf Schnetzke18Isabelle Krämer19Kai Wille20Alexander Hasse21Bastian von Tresckow22Mathias Hänel23Christian Koenecke24Giuliano Filippini Velazquez25Andreas Viardot26Christoph Schmid27Lorenz Thurner28Dominik Wolf29Marion Subklewe30Martin Dreyling31Peter Dreger32Sascha Dietrich33Ulrich Keller34Ulrich Jäger35Richard Greil36Thomas Pabst37Georg Lenz38Björn Chapuy39Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Muenster, Münster, GermanyDepartment of Hematology, Oncology, and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyDepartment of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Muenster, Münster, GermanyDepartment of Hematology, Oncology, and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanySalzburg Cancer Research Institute, Center for Clinical Cancer and Immunology Trials, Salzburg, Austria; Austrian Group for Medical Tumor Therapy Study Group, Vienna, Austria; Third Medical Department with Hematology, Medical Oncology, Rheumatology and Infectiology, Paracelsus Medical University, Salzburg, Austria; Cancer Cluster, Salzburg, AustriaDepartment I of Internal Medicine, Medical Faculty and University Hospital of Cologne, University of Cologne, Cologne, GermanyDepartment of Hematology, University Hospital Inselspital and University of Bern, Bern, SwitzerlandDivision of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, AustriaDepartment of Hematology and Medical Oncology, and INDIGHO Laboratory, University Medical Center Göttingen, Göttingen, GermanyDepartment of Hematology, Oncology, and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyDepartment of Hematology, Oncology, and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyDepartment of Hematolgy, Oncology and Immunology, University Hospital of Düsseldorf, Düsseldorf, GermanyDepartment of Hematology and Oncology, University Hospital Heidelberg, Heidelberg, GermanyInternal Medicine I: Medical Oncology and Hematology, Ordensklinikum Linz GmbH, Elisabethinen, Linz, AustriaDepartment of Hematology, Cell Therapy, Hemostaseology and Infectious Diseases, University Hospital Leipzig, Leipzig, GermanyClinic for Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Tyrolean Cancer Research Institute, Medical University Innsbruck, Innsbruck, AustriaClinic for Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Tyrolean Cancer Research Institute, Medical University Innsbruck, Innsbruck, AustriaDepartment of Medicine III, University Hospital, Ludwig-Maximilians-University Munich, Munich, GermanyHematology and Medical Oncology, University Hospital Jena, Jena, GermanyDepartment of Hematology and Oncology, University Hospital Heidelberg, Heidelberg, GermanyUniversity Clinic for Haematology, Oncology, Hemostaseology and Palliative Care, Johannes Wesling Medical Center Minden, University Hospital of the University of Bochum, Minden, GermanyDepartment of Internal Medicine 1-Oncology, Hematology, Clinical Immunology, and Rheumatology, Saarland University Medical School, Homburg, GermanyDepartment of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Essen, GermanyDepartment of Internal Medicine III, Klinikum Chemnitz, Chemnitz, GermanyDepartment of Hematology and Oncology, University Hospital Hannover, Hannover, GermanyDepartment of Hematology, University Hospital Augsburg, Augsburg, GermanyDepartment of Internal Medicine III, University Hospital of Ulm, Ulm, GermanyDepartment of Hematology, University Hospital Augsburg, Augsburg, GermanyDepartment of Internal Medicine 1-Oncology, Hematology, Clinical Immunology, and Rheumatology, Saarland University Medical School, Homburg, GermanyClinic for Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Tyrolean Cancer Research Institute, Medical University Innsbruck, Innsbruck, AustriaDepartment of Medicine III, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany; German Cancer Consortium (DKTK), Munich, GermanyDepartment of Medicine III, University Hospital, Ludwig-Maximilians-University Munich, Munich, GermanyDepartment of Hematology and Oncology, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Hematolgy, Oncology and Immunology, University Hospital of Düsseldorf, Düsseldorf, GermanyDepartment of Hematology, Oncology, and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Cancer Consortium (DKTK), Berlin, GermanyDivision of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, AustriaSalzburg Cancer Research Institute, Center for Clinical Cancer and Immunology Trials, Salzburg, Austria; Austrian Group for Medical Tumor Therapy Study Group, Vienna, Austria; Third Medical Department with Hematology, Medical Oncology, Rheumatology and Infectiology, Paracelsus Medical University, Salzburg, Austria; Cancer Cluster, Salzburg, AustriaDepartment of Oncology, University Hospital Inselspital and University of Bern, Bern, SwitzerlandDepartment of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Muenster, Münster, GermanyDepartment of Hematology, Oncology, and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Cancer Consortium (DKTK), Berlin, Germany; Correspondence: Björn Chapuy, Charité-University Medical Center, Berlin Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany;Abstract: Glofitamab, a bispecific antibody targeting CD20 and CD3, is approved for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) after at least 2 prior treatment lines, but real-world data are scarce. In this retrospective, multicenter, multinational study, we evaluated the outcomes of 70 patients with r/r DLBCL treated with glofitamab as part of the compassionate use patient program in Germany, Austria, and Switzerland. The median number of prior treatment lines was 4, with 71% of patients refractory to their last treatment. Cytokine release syndrome was observed in 40% of patients (grade 3-4 in 2%), immune effector cell–associated neurotoxicity syndrome in 10% (grade 3 in 1%), and infections in 31% (grade 5 in 3%). The overall response rate was 46%, with 27% achieving complete responses (CR) and 19% partial responses. The median progression-free survival (PFS) was 3.6 months, whereas the median overall survival was 5.7 months. Notably, 13 patients (19%) were in CR 6 months after initiating glofitamab and exhibited durable responses. Elevated lactate dehydrogenase is the most robust predictor of inferior outcome. Patients pretreated with bendamustine within 6 months prior to glofitamab initiation exhibited significantly reduced PFS, suggesting that bendamustine may impair T-cell fitness and hence glofitamab efficacy. In summary, glofitamab demonstrates promising efficacy and a manageable safety profile in heavily pretreated patients with r/r DLBCL in a real-world scenario and the optimal sequence of treatments should use T-cell–depleting agents before glofitamab with caution.http://www.sciencedirect.com/science/article/pii/S2473952924007195 |
| spellingShingle | Evgenii Shumilov Rebecca Wurm-Kuczera Andrea Kerkhoff Meng Wang Thomas Melchardt Udo Holtick Ulrike Bacher Philipp Staber Paolo Mazzeo Corinna Leng David Böckle Alexander Hölscher Joseph Kauer Natalia Rotter Vladan Vucinic Jakob Rudzki David Nachbaur Veit Bücklein Ulf Schnetzke Isabelle Krämer Kai Wille Alexander Hasse Bastian von Tresckow Mathias Hänel Christian Koenecke Giuliano Filippini Velazquez Andreas Viardot Christoph Schmid Lorenz Thurner Dominik Wolf Marion Subklewe Martin Dreyling Peter Dreger Sascha Dietrich Ulrich Keller Ulrich Jäger Richard Greil Thomas Pabst Georg Lenz Björn Chapuy Safety and efficacy of glofitamab for relapsed/refractory large B-cell lymphoma in a multinational real-world study Blood Advances |
| title | Safety and efficacy of glofitamab for relapsed/refractory large B-cell lymphoma in a multinational real-world study |
| title_full | Safety and efficacy of glofitamab for relapsed/refractory large B-cell lymphoma in a multinational real-world study |
| title_fullStr | Safety and efficacy of glofitamab for relapsed/refractory large B-cell lymphoma in a multinational real-world study |
| title_full_unstemmed | Safety and efficacy of glofitamab for relapsed/refractory large B-cell lymphoma in a multinational real-world study |
| title_short | Safety and efficacy of glofitamab for relapsed/refractory large B-cell lymphoma in a multinational real-world study |
| title_sort | safety and efficacy of glofitamab for relapsed refractory large b cell lymphoma in a multinational real world study |
| url | http://www.sciencedirect.com/science/article/pii/S2473952924007195 |
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