Relapsed Philadelphia chromosome‐positive B‐cell acute lymphoblastic leukaemia responds well to a combination of modified hyper‐CVAD, blinatumomab and tyrosine kinase inhibitor

Abstract Introduction Adults with relapsed or refractory Philadelphia chromosome‐positive B‐cell precursor acute lymphoblastic leukaemia (R/R Ph+ BCP‐ALL) have a dismal outcome. Blinatumomab as a single agent has shown activity in R/R Ph‐ BCP‐ALL, and second or third‐generation tyrosine kinase inhib...

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Main Authors: Gaétan Basile, Jean Galtier, Titouan Cazaubiel, Edouard Forcade, Emilie Klein, Audrey Bidet, Carmen Botella‐Garcia, Clémence Mediavilla, Laurence Clement, Pierre‐Yves Dumas, Arnaud Pigneux, Thibaut Leguay
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Language:English
Published: Wiley 2025-02-01
Series:eJHaem
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Online Access:https://doi.org/10.1002/jha2.1064
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author Gaétan Basile
Jean Galtier
Titouan Cazaubiel
Edouard Forcade
Emilie Klein
Audrey Bidet
Carmen Botella‐Garcia
Clémence Mediavilla
Laurence Clement
Pierre‐Yves Dumas
Arnaud Pigneux
Thibaut Leguay
author_facet Gaétan Basile
Jean Galtier
Titouan Cazaubiel
Edouard Forcade
Emilie Klein
Audrey Bidet
Carmen Botella‐Garcia
Clémence Mediavilla
Laurence Clement
Pierre‐Yves Dumas
Arnaud Pigneux
Thibaut Leguay
author_sort Gaétan Basile
collection DOAJ
description Abstract Introduction Adults with relapsed or refractory Philadelphia chromosome‐positive B‐cell precursor acute lymphoblastic leukaemia (R/R Ph+ BCP‐ALL) have a dismal outcome. Blinatumomab as a single agent has shown activity in R/R Ph‐ BCP‐ALL, and second or third‐generation tyrosine kinase inhibitors (TKIs) can produce high remission rates in Ph+ leukaemias. We aimed to assess the activity of blinatumomab and TKI in combination with intensive chemotherapy in the relapsed or refractory setting. Methods Ten patients with R/R Ph+ BCP‐ALL were treated with the combination of a modified hyper‐CVAD (mHCVAD) regimen (cyclophosphamide, vincristine, adriamycin, dexamethasone), blinatumomab and TKI (mainly ponatinib). Results Complete remission (CR) was achieved in 10/10 patients, with deep molecular responses, and 6/10 were alive in remission after a median follow‐up of 19.4 months. Three major cardiovascular events were noted. Conclusion These preliminary data, suggest that the mHCVAD‐blinatumomab‐TKI (mainly ponatinib) regimen may achieve a high rate of CR with undetectable measurable residual disease in adults with R/R Ph+ BCP‐ALL and could be proposed to such patients, but cardiovascular or infectious complications should be warning, especially in older or frail patients.
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spelling doaj-art-e43f55aa9e654f96b7dfca051c5464002025-08-20T02:46:50ZengWileyeJHaem2688-61462025-02-0161n/an/a10.1002/jha2.1064Relapsed Philadelphia chromosome‐positive B‐cell acute lymphoblastic leukaemia responds well to a combination of modified hyper‐CVAD, blinatumomab and tyrosine kinase inhibitorGaétan Basile0Jean Galtier1Titouan Cazaubiel2Edouard Forcade3Emilie Klein4Audrey Bidet5Carmen Botella‐Garcia6Clémence Mediavilla7Laurence Clement8Pierre‐Yves Dumas9Arnaud Pigneux10Thibaut Leguay11Service d'Hématologie Clinique et de Thérapie Cellulaire CHU de Bordeaux Pessac Nouvelle‐Aquitaine FranceService d'Hématologie Clinique et de Thérapie Cellulaire CHU de Bordeaux Pessac Nouvelle‐Aquitaine FranceService d'Hématologie Clinique et de Thérapie Cellulaire CHU de Bordeaux Pessac Nouvelle‐Aquitaine FranceService d'Hématologie Clinique et de Thérapie Cellulaire CHU de Bordeaux Pessac Nouvelle‐Aquitaine FranceService d'Hématologie Biologique CHU de Bordeaux Pessac Nouvelle‐Aquitaine FranceService d'Hématologie Biologique CHU de Bordeaux Pessac Nouvelle‐Aquitaine FranceService d'Hématologie Clinique et de Thérapie Cellulaire CHU de Bordeaux Pessac Nouvelle‐Aquitaine FranceService d'Hématologie Clinique et de Thérapie Cellulaire CHU de Bordeaux Pessac Nouvelle‐Aquitaine FranceService d'Hématologie Clinique et de Thérapie Cellulaire CHU de Bordeaux Pessac Nouvelle‐Aquitaine FranceService d'Hématologie Clinique et de Thérapie Cellulaire CHU de Bordeaux Pessac Nouvelle‐Aquitaine FranceService d'Hématologie Clinique et de Thérapie Cellulaire CHU de Bordeaux Pessac Nouvelle‐Aquitaine FranceService d'Hématologie Clinique et de Thérapie Cellulaire CHU de Bordeaux Pessac Nouvelle‐Aquitaine FranceAbstract Introduction Adults with relapsed or refractory Philadelphia chromosome‐positive B‐cell precursor acute lymphoblastic leukaemia (R/R Ph+ BCP‐ALL) have a dismal outcome. Blinatumomab as a single agent has shown activity in R/R Ph‐ BCP‐ALL, and second or third‐generation tyrosine kinase inhibitors (TKIs) can produce high remission rates in Ph+ leukaemias. We aimed to assess the activity of blinatumomab and TKI in combination with intensive chemotherapy in the relapsed or refractory setting. Methods Ten patients with R/R Ph+ BCP‐ALL were treated with the combination of a modified hyper‐CVAD (mHCVAD) regimen (cyclophosphamide, vincristine, adriamycin, dexamethasone), blinatumomab and TKI (mainly ponatinib). Results Complete remission (CR) was achieved in 10/10 patients, with deep molecular responses, and 6/10 were alive in remission after a median follow‐up of 19.4 months. Three major cardiovascular events were noted. Conclusion These preliminary data, suggest that the mHCVAD‐blinatumomab‐TKI (mainly ponatinib) regimen may achieve a high rate of CR with undetectable measurable residual disease in adults with R/R Ph+ BCP‐ALL and could be proposed to such patients, but cardiovascular or infectious complications should be warning, especially in older or frail patients.https://doi.org/10.1002/jha2.1064acute leukaemiaALLimmunotherapytyrosine kinases
spellingShingle Gaétan Basile
Jean Galtier
Titouan Cazaubiel
Edouard Forcade
Emilie Klein
Audrey Bidet
Carmen Botella‐Garcia
Clémence Mediavilla
Laurence Clement
Pierre‐Yves Dumas
Arnaud Pigneux
Thibaut Leguay
Relapsed Philadelphia chromosome‐positive B‐cell acute lymphoblastic leukaemia responds well to a combination of modified hyper‐CVAD, blinatumomab and tyrosine kinase inhibitor
eJHaem
acute leukaemia
ALL
immunotherapy
tyrosine kinases
title Relapsed Philadelphia chromosome‐positive B‐cell acute lymphoblastic leukaemia responds well to a combination of modified hyper‐CVAD, blinatumomab and tyrosine kinase inhibitor
title_full Relapsed Philadelphia chromosome‐positive B‐cell acute lymphoblastic leukaemia responds well to a combination of modified hyper‐CVAD, blinatumomab and tyrosine kinase inhibitor
title_fullStr Relapsed Philadelphia chromosome‐positive B‐cell acute lymphoblastic leukaemia responds well to a combination of modified hyper‐CVAD, blinatumomab and tyrosine kinase inhibitor
title_full_unstemmed Relapsed Philadelphia chromosome‐positive B‐cell acute lymphoblastic leukaemia responds well to a combination of modified hyper‐CVAD, blinatumomab and tyrosine kinase inhibitor
title_short Relapsed Philadelphia chromosome‐positive B‐cell acute lymphoblastic leukaemia responds well to a combination of modified hyper‐CVAD, blinatumomab and tyrosine kinase inhibitor
title_sort relapsed philadelphia chromosome positive b cell acute lymphoblastic leukaemia responds well to a combination of modified hyper cvad blinatumomab and tyrosine kinase inhibitor
topic acute leukaemia
ALL
immunotherapy
tyrosine kinases
url https://doi.org/10.1002/jha2.1064
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