Bridging intensity is associated with impaired hematopoietic recovery after BCMA CAR-T therapy for multiple myeloma
Abstract: Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy represents a major advance in the treatment of relapsed/refractory multiple myeloma (RRMM). However, the long time span from leukapheresis to actual CAR-T infusion often necessitates bridging therapies. Because of limited knowledge abo...
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Elsevier
2025-08-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S247395292500240X |
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| author | Jan H. Frenking Xiang Zhou Kai Rejeski Vivien Wagner Patrick Costello Thomas Hielscher Lilan Gatti Joseph Kauer Omar Nadeem Elias K. Mai Christian S. Michel Mirco J. Friedrich David Sedloev Niels Weinhold Hartmut Goldschmidt Klaus Herfarth Anita Schmitt Michael Hundemer Michael Schmitt Carsten Müller-Tidow Max Topp Hermann Einsele Peter Dreger Nikhil C. Munshi Adam S. Sperling Leo Rasche Sandra Sauer Marc S. Raab |
| author_facet | Jan H. Frenking Xiang Zhou Kai Rejeski Vivien Wagner Patrick Costello Thomas Hielscher Lilan Gatti Joseph Kauer Omar Nadeem Elias K. Mai Christian S. Michel Mirco J. Friedrich David Sedloev Niels Weinhold Hartmut Goldschmidt Klaus Herfarth Anita Schmitt Michael Hundemer Michael Schmitt Carsten Müller-Tidow Max Topp Hermann Einsele Peter Dreger Nikhil C. Munshi Adam S. Sperling Leo Rasche Sandra Sauer Marc S. Raab |
| author_sort | Jan H. Frenking |
| collection | DOAJ |
| description | Abstract: Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy represents a major advance in the treatment of relapsed/refractory multiple myeloma (RRMM). However, the long time span from leukapheresis to actual CAR-T infusion often necessitates bridging therapies. Because of limited knowledge about the effects of bridging on post–CAR-T clinical course and outcomes, the selection of treatment options is challenging. In this multicenter international observational study, we explored the impact of bridging therapy on hematopoietic reconstitution in 158 patients with RRMM treated with B-cell maturation antigen (BCMA)–directed CAR-T therapy. Based on exposure to classical cytotoxic (CTX) chemotherapy, we classified bridging regimens as non-CTX, intermediate CTX (1-2 CTX agents), or intensive CTX (≥3 CTX agents or high-dose therapy with stem cell transplantation). We found associations between the number of CTX agents used and impaired post–CAR-T hematopoietic reconstitution, evident across hematopoietic cell lineages and particularly manifesting during the late post–CAR-T period. Intensive CTX bridging was associated with a prolonged time to neutrophil and platelet recovery, distinct patterns of hematopoietic recovery (eg, an intermittent phenotype characterized by a second drop), an increased susceptibility to severe infections and a significantly increased risk for severe late cytopenias in univariate and multivariate models. Taken together, these results highlight that bridging intensity distinctly shapes the trajectory of hematopoietic recovery after BCMA CAR-T therapy. Targeted and novel immunotherapies could provide alternatives for bridging, and high-risk patients may particularly benefit from enhanced monitoring, prophylaxis, and supportive care. |
| format | Article |
| id | doaj-art-28e495f6597b4cf48397a0401887b5be |
| institution | DOAJ |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-28e495f6597b4cf48397a0401887b5be2025-08-20T03:04:46ZengElsevierBlood Advances2473-95292025-08-019164151416610.1182/bloodadvances.2024015732Bridging intensity is associated with impaired hematopoietic recovery after BCMA CAR-T therapy for multiple myelomaJan H. Frenking0Xiang Zhou1Kai Rejeski2Vivien Wagner3Patrick Costello4Thomas Hielscher5Lilan Gatti6Joseph Kauer7Omar Nadeem8Elias K. Mai9Christian S. Michel10Mirco J. Friedrich11David Sedloev12Niels Weinhold13Hartmut Goldschmidt14Klaus Herfarth15Anita Schmitt16Michael Hundemer17Michael Schmitt18Carsten Müller-Tidow19Max Topp20Hermann Einsele21Peter Dreger22Nikhil C. Munshi23Adam S. Sperling24Leo Rasche25Sandra Sauer26Marc S. Raab27Heidelberg Myeloma Center, Department of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany; Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center, Heidelberg, Germany; Correspondence: Jan H. Frenking, Internal Medicine V, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany;Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, GermanyAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine III - Hematology/Oncology, LMU University Hospital, Ludwig Maximilian University of Munich, Munich, GermanyDepartment of Internal Medicine II, University Hospital of Würzburg, Würzburg, GermanyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MADivision of Biostatistics, German Cancer Research Center, Heidelberg, GermanyHeidelberg Myeloma Center, Department of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, GermanyHeidelberg Myeloma Center, Department of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany; Molecular Medicine Partnership Unit, Heidelberg, GermanyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MAHeidelberg Myeloma Center, Department of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, GermanyDepartment of Internal Medicine III, University Medical Center Mainz, Mainz, GermanyHeidelberg Myeloma Center, Department of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany; Broad Institute of MIT and Harvard, Cambridge, MAHeidelberg Myeloma Center, Department of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, GermanyHeidelberg Myeloma Center, Department of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany; Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center, Heidelberg, GermanyHeidelberg Myeloma Center, Department of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany; National Center for Tumor Diseases, Heidelberg, GermanyNational Center for Tumor Diseases, Heidelberg, Germany; Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, GermanyHeidelberg Myeloma Center, Department of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, GermanyHeidelberg Myeloma Center, Department of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, GermanyHeidelberg Myeloma Center, Department of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, GermanyHeidelberg Myeloma Center, Department of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany; Molecular Medicine Partnership Unit, Heidelberg, Germany; National Center for Tumor Diseases, Heidelberg, GermanyDepartment of Internal Medicine II, University Hospital of Würzburg, Würzburg, GermanyDepartment of Internal Medicine II, University Hospital of Würzburg, Würzburg, GermanyHeidelberg Myeloma Center, Department of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, GermanyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MADepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Broad Institute of MIT and Harvard, Cambridge, MA; Division of Hematology, Brigham and Women’s Hospital, Boston, MADepartment of Internal Medicine II, University Hospital of Würzburg, Würzburg, GermanyHeidelberg Myeloma Center, Department of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, GermanyHeidelberg Myeloma Center, Department of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany; Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center, Heidelberg, Germany; National Center for Tumor Diseases, Heidelberg, Germany; Marc S. Raab, Internal Medicine V, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany;Abstract: Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy represents a major advance in the treatment of relapsed/refractory multiple myeloma (RRMM). However, the long time span from leukapheresis to actual CAR-T infusion often necessitates bridging therapies. Because of limited knowledge about the effects of bridging on post–CAR-T clinical course and outcomes, the selection of treatment options is challenging. In this multicenter international observational study, we explored the impact of bridging therapy on hematopoietic reconstitution in 158 patients with RRMM treated with B-cell maturation antigen (BCMA)–directed CAR-T therapy. Based on exposure to classical cytotoxic (CTX) chemotherapy, we classified bridging regimens as non-CTX, intermediate CTX (1-2 CTX agents), or intensive CTX (≥3 CTX agents or high-dose therapy with stem cell transplantation). We found associations between the number of CTX agents used and impaired post–CAR-T hematopoietic reconstitution, evident across hematopoietic cell lineages and particularly manifesting during the late post–CAR-T period. Intensive CTX bridging was associated with a prolonged time to neutrophil and platelet recovery, distinct patterns of hematopoietic recovery (eg, an intermittent phenotype characterized by a second drop), an increased susceptibility to severe infections and a significantly increased risk for severe late cytopenias in univariate and multivariate models. Taken together, these results highlight that bridging intensity distinctly shapes the trajectory of hematopoietic recovery after BCMA CAR-T therapy. Targeted and novel immunotherapies could provide alternatives for bridging, and high-risk patients may particularly benefit from enhanced monitoring, prophylaxis, and supportive care.http://www.sciencedirect.com/science/article/pii/S247395292500240X |
| spellingShingle | Jan H. Frenking Xiang Zhou Kai Rejeski Vivien Wagner Patrick Costello Thomas Hielscher Lilan Gatti Joseph Kauer Omar Nadeem Elias K. Mai Christian S. Michel Mirco J. Friedrich David Sedloev Niels Weinhold Hartmut Goldschmidt Klaus Herfarth Anita Schmitt Michael Hundemer Michael Schmitt Carsten Müller-Tidow Max Topp Hermann Einsele Peter Dreger Nikhil C. Munshi Adam S. Sperling Leo Rasche Sandra Sauer Marc S. Raab Bridging intensity is associated with impaired hematopoietic recovery after BCMA CAR-T therapy for multiple myeloma Blood Advances |
| title | Bridging intensity is associated with impaired hematopoietic recovery after BCMA CAR-T therapy for multiple myeloma |
| title_full | Bridging intensity is associated with impaired hematopoietic recovery after BCMA CAR-T therapy for multiple myeloma |
| title_fullStr | Bridging intensity is associated with impaired hematopoietic recovery after BCMA CAR-T therapy for multiple myeloma |
| title_full_unstemmed | Bridging intensity is associated with impaired hematopoietic recovery after BCMA CAR-T therapy for multiple myeloma |
| title_short | Bridging intensity is associated with impaired hematopoietic recovery after BCMA CAR-T therapy for multiple myeloma |
| title_sort | bridging intensity is associated with impaired hematopoietic recovery after bcma car t therapy for multiple myeloma |
| url | http://www.sciencedirect.com/science/article/pii/S247395292500240X |
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