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Results of the European survey on the assessment of deep molecular response in chronic phase CML patients during tyrosine kinase inhibitor therapy (EUREKA registry)

Results of the European survey on the assessment of deep molecular response in chronic phase CML patients during tyrosine kinase inhibitor therapy (EUREKA registry)
Results of the European survey on the assessment of deep molecular response in chronic phase CML patients during tyrosine kinase inhibitor therapy (EUREKA registry)
Purpose: the advent of tyrosine kinase inhibitor (TKI) therapies has revolutionized the treatment of chronic myeloid leukemia (CML). The European LeukemiaNet (ELN) recommends quantification of BCR–ABL1 transcripts by real-time quantitative PCR every three months during TKI treatment. Since a proportion of patients in deep molecular response (DMR: MR4, MR4.5, MR5 ) maintain remission after treatment stop,assessment of DMR is crucial. However, systematically collected molecular data,monitored with sensitive standardized assays, are not available outside clinical trials. Methods: data were collected on the standardized assessment of molecular response in the context of real life practice. BCR-ABL1 transcript levels after >2 years of TKI therapy were evaluated for DMR. Since standardized molecular monitoring is a prerequisite for treatment discontinuation, central surveillance of the performance of the participating laboratories was carried out. Results: between 2014-2017, 3,377 peripheral blood samples from 1,117 CML patients were shipped to 11 standardized reference laboratories in six European countries. BCRABL1 transcript types were b3a2 (41.63%), b2a2 (29.99%), b2a2/b3a2 (3.58%) and atypical (0.54%). For 23.72% of patients, the initial transcript type had not been reported. Response levels (EUTOS laboratory) were: no MMR, n=197 (6.51%); MMR, n=496 (16.40%); MR4 , n=685 (22.64%); MR4.5, n=937 (30.98%); MR5 , n=710 (23.47%). With a Cohen’s kappa coefficient of 0.708, a substantial agreement between EUTOScertified and local laboratories was shown. Conclusions: multicenter DMR assessment is feasible in the context of real life clinical practice in Europe. Information on the BCR-ABL1 transcript type at diagnosis is crucial to accurately monitor patients’ molecular response during or after TKI therapy
0171-5216
1-6
Mobius, Susanne
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Schenk, Thomas
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Himsel, Danny
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Maier, Jacqueline
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Franke, Georg-Nikolaus
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Saussele, Susanne
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Pott, Christianne
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Andrikovics, Hajnalka
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Meggyesi, Nora
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Machova-Polakova, Katerina
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Zizkova, Hana
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Jurcek, Tomas
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Mesanovic, Semir
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Zadro, Renata
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Gottardi, Enrico
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Haenig, Jens
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Schuld, Peter
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Cross, Nicholas
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Hochhaus, Andreas
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Ernst, Thomas
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Mobius, Susanne
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Schenk, Thomas
72563dc5-52aa-429b-a647-081c6d3486bf
Himsel, Danny
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Maier, Jacqueline
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Franke, Georg-Nikolaus
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Saussele, Susanne
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Pott, Christianne
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Andrikovics, Hajnalka
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Meggyesi, Nora
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Machova-Polakova, Katerina
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Zizkova, Hana
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Jurcek, Tomas
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Mesanovic, Semir
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Zadro, Renata
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Gottardi, Enrico
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Haenig, Jens
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Schuld, Peter
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Cross, Nicholas
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Hochhaus, Andreas
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Ernst, Thomas
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Mobius, Susanne, Schenk, Thomas, Himsel, Danny, Maier, Jacqueline, Franke, Georg-Nikolaus, Saussele, Susanne, Pott, Christianne, Andrikovics, Hajnalka, Meggyesi, Nora, Machova-Polakova, Katerina, Zizkova, Hana, Jurcek, Tomas, Mesanovic, Semir, Zadro, Renata, Gottardi, Enrico, Haenig, Jens, Schuld, Peter, Cross, Nicholas, Hochhaus, Andreas and Ernst, Thomas (2019) Results of the European survey on the assessment of deep molecular response in chronic phase CML patients during tyrosine kinase inhibitor therapy (EUREKA registry). Journal of Cancer Research and Clinical Oncology, 1-6. (doi:10.1007/s00432-019-02910-6).

Record type: Article

Abstract

Purpose: the advent of tyrosine kinase inhibitor (TKI) therapies has revolutionized the treatment of chronic myeloid leukemia (CML). The European LeukemiaNet (ELN) recommends quantification of BCR–ABL1 transcripts by real-time quantitative PCR every three months during TKI treatment. Since a proportion of patients in deep molecular response (DMR: MR4, MR4.5, MR5 ) maintain remission after treatment stop,assessment of DMR is crucial. However, systematically collected molecular data,monitored with sensitive standardized assays, are not available outside clinical trials. Methods: data were collected on the standardized assessment of molecular response in the context of real life practice. BCR-ABL1 transcript levels after >2 years of TKI therapy were evaluated for DMR. Since standardized molecular monitoring is a prerequisite for treatment discontinuation, central surveillance of the performance of the participating laboratories was carried out. Results: between 2014-2017, 3,377 peripheral blood samples from 1,117 CML patients were shipped to 11 standardized reference laboratories in six European countries. BCRABL1 transcript types were b3a2 (41.63%), b2a2 (29.99%), b2a2/b3a2 (3.58%) and atypical (0.54%). For 23.72% of patients, the initial transcript type had not been reported. Response levels (EUTOS laboratory) were: no MMR, n=197 (6.51%); MMR, n=496 (16.40%); MR4 , n=685 (22.64%); MR4.5, n=937 (30.98%); MR5 , n=710 (23.47%). With a Cohen’s kappa coefficient of 0.708, a substantial agreement between EUTOScertified and local laboratories was shown. Conclusions: multicenter DMR assessment is feasible in the context of real life clinical practice in Europe. Information on the BCR-ABL1 transcript type at diagnosis is crucial to accurately monitor patients’ molecular response during or after TKI therapy

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Accepted/In Press date: 26 March 2019
e-pub ahead of print date: 2 April 2019

Identifiers

Local EPrints ID: 429632
URI: http://eprints.soton.ac.uk/id/eprint/429632
ISSN: 0171-5216
PURE UUID: 295c109b-dd04-412a-9f39-1d537f0b5bdc
ORCID for Nicholas Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 02 Apr 2019 16:30
Last modified: 16 Mar 2024 07:43

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Contributors

Author: Susanne Mobius
Author: Thomas Schenk
Author: Danny Himsel
Author: Jacqueline Maier
Author: Georg-Nikolaus Franke
Author: Susanne Saussele
Author: Christianne Pott
Author: Hajnalka Andrikovics
Author: Nora Meggyesi
Author: Katerina Machova-Polakova
Author: Hana Zizkova
Author: Tomas Jurcek
Author: Semir Mesanovic
Author: Renata Zadro
Author: Enrico Gottardi
Author: Jens Haenig
Author: Peter Schuld
Author: Nicholas Cross ORCID iD
Author: Andreas Hochhaus
Author: Thomas Ernst

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