Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784836090941669376
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
work_keys_str_mv AT marschollekpaweł blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT liszkakarolina blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT mielcareksiedziukmonika blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT rybkablanka blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT ryczankrawczykrenata blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT panasiukanna blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT olejnikigor blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT fraczkiewiczjowita blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT dachowskakałwakiwona blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT miziamalarzagnieszka blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT szczepanskitomasz blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT młynarskiwojciech blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT styczynskijan blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT drabkokatarzyna blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT karolczykgrazyna blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT gorczynskaewa blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT maciejzauchajan blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden
AT kałwakkrzysztof blinatumomabpriortocartcelltherapyatreatmentoptionworthconsiderationforhighdiseaseburden