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Blinatumomab Prior to CAR-T Cell Therapy—A Treatment Option Worth Consideration for High Disease Burden
The optimal bridging therapy before CAR-T cell infusion in pediatric relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL) still remains an open question. The administration of blinatumomab prior to CAR-T therapy is controversial since a potential loss of CD19+ target ce...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687755/ https://www.ncbi.nlm.nih.gov/pubmed/36428483 http://dx.doi.org/10.3390/biomedicines10112915 |
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author | Marschollek, Paweł Liszka, Karolina Mielcarek-Siedziuk, Monika Rybka, Blanka Ryczan-Krawczyk, Renata Panasiuk, Anna Olejnik, Igor Frączkiewicz, Jowita Dachowska-Kałwak, Iwona Mizia-Malarz, Agnieszka Szczepański, Tomasz Młynarski, Wojciech Styczyński, Jan Drabko, Katarzyna Karolczyk, Grażyna Gorczyńska, Ewa Maciej Zaucha, Jan Kałwak, Krzysztof |
author_facet | Marschollek, Paweł Liszka, Karolina Mielcarek-Siedziuk, Monika Rybka, Blanka Ryczan-Krawczyk, Renata Panasiuk, Anna Olejnik, Igor Frączkiewicz, Jowita Dachowska-Kałwak, Iwona Mizia-Malarz, Agnieszka Szczepański, Tomasz Młynarski, Wojciech Styczyński, Jan Drabko, Katarzyna Karolczyk, Grażyna Gorczyńska, Ewa Maciej Zaucha, Jan Kałwak, Krzysztof |
author_sort | Marschollek, Paweł |
collection | PubMed |
description | The optimal bridging therapy before CAR-T cell infusion in pediatric relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL) still remains an open question. The administration of blinatumomab prior to CAR-T therapy is controversial since a potential loss of CD19+ target cells may negatively impact the activation, persistence, and, as a consequence, the efficacy of subsequently used CAR-T cells. Here, we report a single-center experience in seven children with chemorefractory BCP-ALL treated with blinatumomab before CAR-T cell therapy either to reduce disease burden before apheresis (six patients) or as a bridging therapy (two patients). All patients responded to blinatumomab except one. At the time of CAR-T cell infusion, all patients were in cytological complete remission (CR). Four patients had low positive PCR-MRD, and the remaining three were MRD-negative. All patients remained in CR at day +28 after CAR-T infusion, and six out of seven patients were MRD-negative. With a median follow-up of 497 days, four patients remain in CR and MRD-negative. Three children relapsed with CD19 negative disease: two of them died, and one, who previously did not respond to blinatumomab, was successfully rescued by stem cell transplant. To conclude, blinatumomab can effectively lower disease burden with fewer side effects than standard chemotherapeutics. Therefore, it may be a valid option for patients with high-disease burden prior to CAR-T cell therapy without clear evidence of compromising efficacy; however, further investigations are necessary. |
format | Online Article Text |
id | pubmed-9687755 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96877552022-11-25 Blinatumomab Prior to CAR-T Cell Therapy—A Treatment Option Worth Consideration for High Disease Burden Marschollek, Paweł Liszka, Karolina Mielcarek-Siedziuk, Monika Rybka, Blanka Ryczan-Krawczyk, Renata Panasiuk, Anna Olejnik, Igor Frączkiewicz, Jowita Dachowska-Kałwak, Iwona Mizia-Malarz, Agnieszka Szczepański, Tomasz Młynarski, Wojciech Styczyński, Jan Drabko, Katarzyna Karolczyk, Grażyna Gorczyńska, Ewa Maciej Zaucha, Jan Kałwak, Krzysztof Biomedicines Article The optimal bridging therapy before CAR-T cell infusion in pediatric relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL) still remains an open question. The administration of blinatumomab prior to CAR-T therapy is controversial since a potential loss of CD19+ target cells may negatively impact the activation, persistence, and, as a consequence, the efficacy of subsequently used CAR-T cells. Here, we report a single-center experience in seven children with chemorefractory BCP-ALL treated with blinatumomab before CAR-T cell therapy either to reduce disease burden before apheresis (six patients) or as a bridging therapy (two patients). All patients responded to blinatumomab except one. At the time of CAR-T cell infusion, all patients were in cytological complete remission (CR). Four patients had low positive PCR-MRD, and the remaining three were MRD-negative. All patients remained in CR at day +28 after CAR-T infusion, and six out of seven patients were MRD-negative. With a median follow-up of 497 days, four patients remain in CR and MRD-negative. Three children relapsed with CD19 negative disease: two of them died, and one, who previously did not respond to blinatumomab, was successfully rescued by stem cell transplant. To conclude, blinatumomab can effectively lower disease burden with fewer side effects than standard chemotherapeutics. Therefore, it may be a valid option for patients with high-disease burden prior to CAR-T cell therapy without clear evidence of compromising efficacy; however, further investigations are necessary. MDPI 2022-11-13 /pmc/articles/PMC9687755/ /pubmed/36428483 http://dx.doi.org/10.3390/biomedicines10112915 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Marschollek, Paweł Liszka, Karolina Mielcarek-Siedziuk, Monika Rybka, Blanka Ryczan-Krawczyk, Renata Panasiuk, Anna Olejnik, Igor Frączkiewicz, Jowita Dachowska-Kałwak, Iwona Mizia-Malarz, Agnieszka Szczepański, Tomasz Młynarski, Wojciech Styczyński, Jan Drabko, Katarzyna Karolczyk, Grażyna Gorczyńska, Ewa Maciej Zaucha, Jan Kałwak, Krzysztof Blinatumomab Prior to CAR-T Cell Therapy—A Treatment Option Worth Consideration for High Disease Burden |
title | Blinatumomab Prior to CAR-T Cell Therapy—A Treatment Option Worth Consideration for High Disease Burden |
title_full | Blinatumomab Prior to CAR-T Cell Therapy—A Treatment Option Worth Consideration for High Disease Burden |
title_fullStr | Blinatumomab Prior to CAR-T Cell Therapy—A Treatment Option Worth Consideration for High Disease Burden |
title_full_unstemmed | Blinatumomab Prior to CAR-T Cell Therapy—A Treatment Option Worth Consideration for High Disease Burden |
title_short | Blinatumomab Prior to CAR-T Cell Therapy—A Treatment Option Worth Consideration for High Disease Burden |
title_sort | blinatumomab prior to car-t cell therapy—a treatment option worth consideration for high disease burden |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687755/ https://www.ncbi.nlm.nih.gov/pubmed/36428483 http://dx.doi.org/10.3390/biomedicines10112915 |
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