Outcomes of bispecific antibody therapy after CAR T-cell failure in relapsed/refractory large B-cell lymphoma
Abstract: Patients with large B-cell lymphoma (LBCL) who experience relapsed disease after CD19-directed chimeric antigen receptor (CAR) T-cell (CAR-T) therapy have a poor prognosis. Bispecific antibodies (BsAbs) induce complete remissions in ∼35% of these cases. Hypothesizing overlapping LBCL-intri...
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Elsevier
2025-08-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952925002289 |
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| author | Evgenii Shumilov Julia Katharina Scholz Maximilian Seib Paolo Mazzeo Rebecca Wurm-Kuczera Vladan Vucinic Udo Holtick Hristo Boyadzhiev Thomas Melchardt Alexander Hölscher Christian Schultze-Florey Atef Abdelhafez Giuliano Filippini Velazquez Anna Ossami Saidy Vadim Lesan Ulf Schnetzke Andrea Kerkhoff Ulrike Bacher Susanne Ghandili Enver Aydilek Niklas Gebauer Thomas Weber Gerald Wulf Bertram Glass Lorenz Thurner Florian H. Heidel Christoph Schmid Andreas Viardot Mathias Hänel Sascha Dietrich Thomas Pabst Francis Ayuk Bastian von Tresckow Björn Chapuy Christiane Pott Fabian Müller Georg Lenz |
| author_facet | Evgenii Shumilov Julia Katharina Scholz Maximilian Seib Paolo Mazzeo Rebecca Wurm-Kuczera Vladan Vucinic Udo Holtick Hristo Boyadzhiev Thomas Melchardt Alexander Hölscher Christian Schultze-Florey Atef Abdelhafez Giuliano Filippini Velazquez Anna Ossami Saidy Vadim Lesan Ulf Schnetzke Andrea Kerkhoff Ulrike Bacher Susanne Ghandili Enver Aydilek Niklas Gebauer Thomas Weber Gerald Wulf Bertram Glass Lorenz Thurner Florian H. Heidel Christoph Schmid Andreas Viardot Mathias Hänel Sascha Dietrich Thomas Pabst Francis Ayuk Bastian von Tresckow Björn Chapuy Christiane Pott Fabian Müller Georg Lenz |
| author_sort | Evgenii Shumilov |
| collection | DOAJ |
| description | Abstract: Patients with large B-cell lymphoma (LBCL) who experience relapsed disease after CD19-directed chimeric antigen receptor (CAR) T-cell (CAR-T) therapy have a poor prognosis. Bispecific antibodies (BsAbs) induce complete remissions in ∼35% of these cases. Hypothesizing overlapping LBCL-intrinsic resistance mechanisms as well as common poor prognosis predictors to CAR-T and BsAb therapy, we conducted a multicenter retrospective analysis including 92 patients with relapsed/refractory (R/R) LBCL treated with BsAbs after CAR-T failure. Overall response rate (ORR) was 43%, with a progression-free survival (PFS) of 2.8 months. Patients receiving BsAbs during early relapse (≤3 months) achieved a significantly worse outcome (ORR, 29%; PFS, 2.2 months) compared with patients with an intermediate (4-6 months; ORR, 54%; PFS, 3.7 months) or a late relapse (>6 months; ORR, 60%; PFS, 10.5 months). The benefit of later relapse was particularly notable in patients receiving BsAbs as first salvage therapy compared with those receiving a BsAb in subsequent lines (PFS not reached vs 2.7 months; overall survival not reached vs 9.1 months, respectively). In addition to early R/R state before BsAbs, elevated lactate dehydrogenase and higher International Prognostic Index score were significant predictors of poor outcomes to BsAb in multivariate Cox regression analyses. The finding that patients with early relapse after CAR-T respond particularly poorly to BsAb highlights the necessity for alternative treatment options in this high-risk patient cohort. |
| format | Article |
| id | doaj-art-84a861fcd92641c38b044eecaa641b5b |
| institution | Kabale University |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-84a861fcd92641c38b044eecaa641b5b2025-08-20T03:33:06ZengElsevierBlood Advances2473-95292025-08-019153955396610.1182/bloodadvances.2024015719Outcomes of bispecific antibody therapy after CAR T-cell failure in relapsed/refractory large B-cell lymphomaEvgenii Shumilov0Julia Katharina Scholz1Maximilian Seib2Paolo Mazzeo3Rebecca Wurm-Kuczera4Vladan Vucinic5Udo Holtick6Hristo Boyadzhiev7Thomas Melchardt8Alexander Hölscher9Christian Schultze-Florey10Atef Abdelhafez11Giuliano Filippini Velazquez12Anna Ossami Saidy13Vadim Lesan14Ulf Schnetzke15Andrea Kerkhoff16Ulrike Bacher17Susanne Ghandili18Enver Aydilek19Niklas Gebauer20Thomas Weber21Gerald Wulf22Bertram Glass23Lorenz Thurner24Florian H. Heidel25Christoph Schmid26Andreas Viardot27Mathias Hänel28Sascha Dietrich29Thomas Pabst30Francis Ayuk31Bastian von Tresckow32Björn Chapuy33Christiane Pott34Fabian Müller35Georg Lenz36Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, Muenster, GermanyDepartment of Internal Medicine 5, Hematology and Oncology, University Hospital of Erlangen, Erlangen, GermanyDepartment of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, Muenster, GermanyDepartment of Hematology and Medical Oncology, University Hospital Göttingen, Göttingen, Germany; Department of Hematology and Medical Oncology, INDIGHO Laboratory, University Medical Center Göttingen, Göttingen, GermanyDepartment of Hematology, Oncology, and Cancer Immunology, Charité-University Medical Center Berlin, Berlin, GermanyDepartment of Hematology, Hemostaseology, Cellular Therapy and Infectiology, University Hospital Leipzig, Leipzig, GermanyDepartment I of Internal Medicine, Medical Faculty and University Hospital of Cologne, University of Cologne, Cologne, GermanyDepartment of Medical Oncology, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland; Habichtswald Hospital, Kassel, GermanyThird Medical Department at the Paracelsus Medical University Salzburg, Cancer Center, Salzburg, Austria; Salzburg Cancer Research Institute, Salzburg, Austria; Austrian Group for Medical Tumor Therapy, Salzburg, Austria; Cancer Cluster, Salzburg, AustriaDepartment of Hematology, Oncology, and Immunology, University Hospital of Duesseldorf, Duesseldorf, GermanyDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyDepartment of Hematology, Oncology, and Cancer Immunology, Charité-University Medical Center Berlin, Berlin, GermanyDepartment of Hematology, University Hospital Augsburg, Augsburg, GermanyDepartment of Hematology, Oncology, and Tumor Immunology, Helios Klinikum Berlin-Buch, Berlin, GermanyDepartment of Internal Medicine 1, Oncology, Hematology, Clinical Immunology, and Rheumatology, Saarland University Medical School, Homburg, GermanyDepartment of Internal Medicine II, Hematology and Medical Oncology, University Hospital Jena, Jena, GermanyDepartment of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, Muenster, GermanyDepartment of Hematology, University Hospital Inselspital and University of Bern, Bern, SwitzerlandDepartment of Oncology, Hematology, and Bone Marrow Transplantation with Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Hematology and Medical Oncology, University Hospital Göttingen, Göttingen, GermanyDepartment for Hematology and Oncology, University Hospital Schleswig-Holstein, Lübeck, GermanyDepartment of Internal Medicine IV, Haematology and Oncology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, Halle, GermanyDepartment of Hematology and Medical Oncology, University Hospital Göttingen, Göttingen, GermanyDepartment of Hematology, Oncology, and Tumor Immunology, Helios Klinikum Berlin-Buch, Berlin, GermanyDepartment of Internal Medicine 1, Oncology, Hematology, Clinical Immunology, and Rheumatology, Saarland University Medical School, Homburg, GermanyDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany; Cellular Therapy Center, Hannover Medical School, Hannover, GermanyDepartment of Hematology, University Hospital Augsburg, Augsburg, GermanyDepartment of Internal Medicine III, University Hospital of Ulm, Ulm, GermanyMedical Clinic III, Klinikum Chemnitz, Chemnitz, GermanyDepartment of Hematology, Oncology, and Immunology, University Hospital of Duesseldorf, Duesseldorf, GermanyDepartment of Medical Oncology, Inselspital, University Hospital Bern, University of Bern, Bern, SwitzerlandDepartment of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Hematology and Stem Cell Transplantation, West German Cancer Center and German Cancer Consortium (Deutsches Konsortium für Translationale Krebsforschung Partner Site Essen), Essen University Hospital, University of Duisburg-Essen, Essen, GermanyDepartment of Hematology, Oncology, and Cancer Immunology, Charité-University Medical Center Berlin, Berlin, GermanyDepartment of Internal Medicine II, University Hospital Schleswig-Holstein, Kiel, GermanyDepartment of Internal Medicine 5, Hematology and Oncology, University Hospital of Erlangen, Erlangen, Germany; Fabian Müller, Department of Internal Medicine 5, Hematology and Oncology, University Hospital of Erlangen, Schwabachanlage 12, 91054 Erlangen, Germany;Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, Muenster, Germany; Correspondence: Georg Lenz, Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Münster, Albert-Schweitzer Campus 1, 48149 Münster, Germany;Abstract: Patients with large B-cell lymphoma (LBCL) who experience relapsed disease after CD19-directed chimeric antigen receptor (CAR) T-cell (CAR-T) therapy have a poor prognosis. Bispecific antibodies (BsAbs) induce complete remissions in ∼35% of these cases. Hypothesizing overlapping LBCL-intrinsic resistance mechanisms as well as common poor prognosis predictors to CAR-T and BsAb therapy, we conducted a multicenter retrospective analysis including 92 patients with relapsed/refractory (R/R) LBCL treated with BsAbs after CAR-T failure. Overall response rate (ORR) was 43%, with a progression-free survival (PFS) of 2.8 months. Patients receiving BsAbs during early relapse (≤3 months) achieved a significantly worse outcome (ORR, 29%; PFS, 2.2 months) compared with patients with an intermediate (4-6 months; ORR, 54%; PFS, 3.7 months) or a late relapse (>6 months; ORR, 60%; PFS, 10.5 months). The benefit of later relapse was particularly notable in patients receiving BsAbs as first salvage therapy compared with those receiving a BsAb in subsequent lines (PFS not reached vs 2.7 months; overall survival not reached vs 9.1 months, respectively). In addition to early R/R state before BsAbs, elevated lactate dehydrogenase and higher International Prognostic Index score were significant predictors of poor outcomes to BsAb in multivariate Cox regression analyses. The finding that patients with early relapse after CAR-T respond particularly poorly to BsAb highlights the necessity for alternative treatment options in this high-risk patient cohort.http://www.sciencedirect.com/science/article/pii/S2473952925002289 |
| spellingShingle | Evgenii Shumilov Julia Katharina Scholz Maximilian Seib Paolo Mazzeo Rebecca Wurm-Kuczera Vladan Vucinic Udo Holtick Hristo Boyadzhiev Thomas Melchardt Alexander Hölscher Christian Schultze-Florey Atef Abdelhafez Giuliano Filippini Velazquez Anna Ossami Saidy Vadim Lesan Ulf Schnetzke Andrea Kerkhoff Ulrike Bacher Susanne Ghandili Enver Aydilek Niklas Gebauer Thomas Weber Gerald Wulf Bertram Glass Lorenz Thurner Florian H. Heidel Christoph Schmid Andreas Viardot Mathias Hänel Sascha Dietrich Thomas Pabst Francis Ayuk Bastian von Tresckow Björn Chapuy Christiane Pott Fabian Müller Georg Lenz Outcomes of bispecific antibody therapy after CAR T-cell failure in relapsed/refractory large B-cell lymphoma Blood Advances |
| title | Outcomes of bispecific antibody therapy after CAR T-cell failure in relapsed/refractory large B-cell lymphoma |
| title_full | Outcomes of bispecific antibody therapy after CAR T-cell failure in relapsed/refractory large B-cell lymphoma |
| title_fullStr | Outcomes of bispecific antibody therapy after CAR T-cell failure in relapsed/refractory large B-cell lymphoma |
| title_full_unstemmed | Outcomes of bispecific antibody therapy after CAR T-cell failure in relapsed/refractory large B-cell lymphoma |
| title_short | Outcomes of bispecific antibody therapy after CAR T-cell failure in relapsed/refractory large B-cell lymphoma |
| title_sort | outcomes of bispecific antibody therapy after car t cell failure in relapsed refractory large b cell lymphoma |
| url | http://www.sciencedirect.com/science/article/pii/S2473952925002289 |
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