Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults
Abstract Anti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusio...
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BMC
2025-01-01
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| Series: | Journal of Hematology & Oncology |
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| Online Access: | https://doi.org/10.1186/s13045-024-01659-x |
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| author | Maike Breidenbach Peter Bader Andishe Attarbaschi Claudia Rossig Roland Meisel Markus Metzler Marion Subklewe Fabian Mueller Paul-Gerhardt Schlegel Irene Teichert von Lüttichau Jean-Pierre Bourquin Gabriele Escherich Gunnar Cario Peter Lang Ramona Coffey Arend von Stackelberg Semjon Willier Brigitte Strahm Christina Peters Tobias Feuchtinger |
| author_facet | Maike Breidenbach Peter Bader Andishe Attarbaschi Claudia Rossig Roland Meisel Markus Metzler Marion Subklewe Fabian Mueller Paul-Gerhardt Schlegel Irene Teichert von Lüttichau Jean-Pierre Bourquin Gabriele Escherich Gunnar Cario Peter Lang Ramona Coffey Arend von Stackelberg Semjon Willier Brigitte Strahm Christina Peters Tobias Feuchtinger |
| author_sort | Maike Breidenbach |
| collection | DOAJ |
| description | Abstract Anti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood. In this retrospective, multinational study, real-world data were collected from 14 different sites in Germany, Austria and Switzerland on 88 patients receiving 93 2nd-generation CAR therapies. Bridging therapy was classified into the categories 1) no systemic therapy (15/93 treatments), 2) low-intensity therapy (38/93 treatments) and 3) high-intensity therapy (39/93 treatments). We analyzed the impact of bridging regimens on clinical outcome. Patients receiving a high-intensity bridging therapy had a significantly higher tumor burden at time of eligibility compared to patients treated with a low-intensity or no systemic bridging therapy. They suffered significantly more from bacterial adverse events and mucositis. Overall survival was significantly better for patients who did not receive any bridging therapy in comparison to patients who had been treated with a low- or high-intensity bridging regimen. In conclusion, in this retrospective cohort, high-intensity bridging therapy has not improved the outcome in terms of overall and progression-free survival in comparison to a low-intensity therapy. Yet, high-intensity bridging therapy was associated with more adverse events. Our study suggests that a low-intensity bridging regimen may be preferred whenever tumor burden and disease kinetics allow this treatment strategy. |
| format | Article |
| id | doaj-art-0263ffd4bac14370ad72a7821af885c6 |
| institution | Kabale University |
| issn | 1756-8722 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj-art-0263ffd4bac14370ad72a7821af885c62025-01-19T12:36:21ZengBMCJournal of Hematology & Oncology1756-87222025-01-011811510.1186/s13045-024-01659-xMultinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adultsMaike Breidenbach0Peter Bader1Andishe Attarbaschi2Claudia Rossig3Roland Meisel4Markus Metzler5Marion Subklewe6Fabian Mueller7Paul-Gerhardt Schlegel8Irene Teichert von Lüttichau9Jean-Pierre Bourquin10Gabriele Escherich11Gunnar Cario12Peter Lang13Ramona Coffey14Arend von Stackelberg15Semjon Willier16Brigitte Strahm17Christina Peters18Tobias Feuchtinger19Bavarian Cancer Research Center (BZKF), R/R ALL Study GroupDepartment of Pediatrics, Division for Stem Cell Transplantation, Immunology and Intensive Care, Goethe University Frankfurt, University HospitalDepartment of Pediatric Hematology and Oncology, St. Anna Children’s HospitalDepartment of Pediatric Hematology and Oncology, University Children’s Hospital MuensterDivision of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-UniversityBavarian Cancer Research Center (BZKF), R/R ALL Study GroupBavarian Cancer Research Center (BZKF), R/R ALL Study GroupBavarian Cancer Research Center (BZKF), R/R ALL Study GroupBavarian Cancer Research Center (BZKF), R/R ALL Study GroupBavarian Cancer Research Center (BZKF), R/R ALL Study GroupDepartment of Oncology and Children’s Research Center, University Children’s Hospital ZurichClinic of Pediatric Hematology and Oncology, University Medical Center Hamburg-EppendorfDepartment of Pediatrics I, University Hospital Schleswig-HolsteinDepartment of General Pediatrics, Hematology and Oncology, University Children’s Hospital TübingenBavarian Cancer Research Center (BZKF), R/R ALL Study GroupDepartment of Pediatric Oncology and Hematology, Charité Universitaetsmedizin BerlinDepartment of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical Center – University of Freiburg, Faculty of Medicine, University of FreiburgDepartment of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical Center – University of Freiburg, Faculty of Medicine, University of FreiburgDepartment of Pediatric Hematology and Oncology, St. Anna Children’s HospitalBavarian Cancer Research Center (BZKF), R/R ALL Study GroupAbstract Anti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood. In this retrospective, multinational study, real-world data were collected from 14 different sites in Germany, Austria and Switzerland on 88 patients receiving 93 2nd-generation CAR therapies. Bridging therapy was classified into the categories 1) no systemic therapy (15/93 treatments), 2) low-intensity therapy (38/93 treatments) and 3) high-intensity therapy (39/93 treatments). We analyzed the impact of bridging regimens on clinical outcome. Patients receiving a high-intensity bridging therapy had a significantly higher tumor burden at time of eligibility compared to patients treated with a low-intensity or no systemic bridging therapy. They suffered significantly more from bacterial adverse events and mucositis. Overall survival was significantly better for patients who did not receive any bridging therapy in comparison to patients who had been treated with a low- or high-intensity bridging regimen. In conclusion, in this retrospective cohort, high-intensity bridging therapy has not improved the outcome in terms of overall and progression-free survival in comparison to a low-intensity therapy. Yet, high-intensity bridging therapy was associated with more adverse events. Our study suggests that a low-intensity bridging regimen may be preferred whenever tumor burden and disease kinetics allow this treatment strategy.https://doi.org/10.1186/s13045-024-01659-xB-ALLCAR T cellsBridging therapy |
| spellingShingle | Maike Breidenbach Peter Bader Andishe Attarbaschi Claudia Rossig Roland Meisel Markus Metzler Marion Subklewe Fabian Mueller Paul-Gerhardt Schlegel Irene Teichert von Lüttichau Jean-Pierre Bourquin Gabriele Escherich Gunnar Cario Peter Lang Ramona Coffey Arend von Stackelberg Semjon Willier Brigitte Strahm Christina Peters Tobias Feuchtinger Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults Journal of Hematology & Oncology B-ALL CAR T cells Bridging therapy |
| title | Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults |
| title_full | Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults |
| title_fullStr | Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults |
| title_full_unstemmed | Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults |
| title_short | Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults |
| title_sort | multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed refractory acute lymphoblastic leukemia in children and young adults |
| topic | B-ALL CAR T cells Bridging therapy |
| url | https://doi.org/10.1186/s13045-024-01659-x |
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