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

Susanne Möbius, Thomas Schenk, Danny Himsel, Jacqueline Maier, Georg Nikolaus Franke, Susanne Saussele, Christiane Pott, H. Andrikovics, Nora Meggyesi, Katerina Machova-Polakova, Hana Zizkova, Tomáš Jurcek, Semir Mesanovic, Renata Zadro, Enrico Gottardi, Jens Haenig, Peter Schuld, Nicholas C.P. Cross, Andreas Hochhaus, Thomas Ernst

Research output: Contribution to journalArticle

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 3 months during TKI treatment. Since a proportion of patients in deep molecular response (DMR: MR 4 , MR 4.5 , MR 5 ) 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 by local laboratories as well as standardized EUTOS laboratories. 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 and 2017, 3377 peripheral blood samples from 1117 CML patients were shipped to 11 standardized reference laboratories in six European countries. BCR–ABL1 transcript types were b3a2 (41.63%), b2a2 (29.99%), b2a2/b3a2 (3.58%) and atypical (0.54%). For 23.72% of the 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%); MR 4 , n = 685 (22.64%); MR 4.5 , n = 937 (30.98%); MR 5 , n = 710 (23.47%). With a Cohen’s kappa coefficient of 0.708, a substantial agreement between EUTOS-certified 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.

Original languageEnglish
JournalJournal of cancer research and clinical oncology
DOIs
Publication statusPublished - Jan 1 2019

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Leukemia, Myeloid, Chronic Phase
Protein-Tyrosine Kinases
Registries
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Therapeutics
Surveys and Questionnaires
Real-Time Polymerase Chain Reaction
Clinical Trials

Keywords

  • BCR–ABL
  • Chronic myeloid leukemia
  • CML
  • Deep molecular remission
  • Eureka
  • Molecular monitoring
  • Standardization
  • TFR
  • Treatment-free remission

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Results of the European survey on the assessment of deep molecular response in chronic phase CML patients during tyrosine kinase inhibitor therapy (EUREKA registry). / Möbius, Susanne; Schenk, Thomas; Himsel, Danny; Maier, Jacqueline; Franke, Georg Nikolaus; Saussele, Susanne; Pott, Christiane; Andrikovics, H.; Meggyesi, Nora; Machova-Polakova, Katerina; Zizkova, Hana; Jurcek, Tomáš; Mesanovic, Semir; Zadro, Renata; Gottardi, Enrico; Haenig, Jens; Schuld, Peter; Cross, Nicholas C.P.; Hochhaus, Andreas; Ernst, Thomas.

In: Journal of cancer research and clinical oncology, 01.01.2019.

Research output: Contribution to journalArticle

Möbius, S, Schenk, T, Himsel, D, Maier, J, Franke, GN, Saussele, S, Pott, C, Andrikovics, H, Meggyesi, N, Machova-Polakova, K, Zizkova, H, Jurcek, T, Mesanovic, S, Zadro, R, Gottardi, E, Haenig, J, Schuld, P, Cross, NCP, Hochhaus, A & Ernst, T 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. https://doi.org/10.1007/s00432-019-02910-6
Möbius, Susanne ; Schenk, Thomas ; Himsel, Danny ; Maier, Jacqueline ; Franke, Georg Nikolaus ; Saussele, Susanne ; Pott, Christiane ; Andrikovics, H. ; Meggyesi, Nora ; Machova-Polakova, Katerina ; Zizkova, Hana ; Jurcek, Tomáš ; Mesanovic, Semir ; Zadro, Renata ; Gottardi, Enrico ; Haenig, Jens ; Schuld, Peter ; Cross, Nicholas C.P. ; Hochhaus, Andreas ; Ernst, Thomas. / Results of the European survey on the assessment of deep molecular response in chronic phase CML patients during tyrosine kinase inhibitor therapy (EUREKA registry). In: Journal of cancer research and clinical oncology. 2019.
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title = "Results of the European survey on the assessment of deep molecular response in chronic phase CML patients during tyrosine kinase inhibitor therapy (EUREKA registry)",
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 3 months during TKI treatment. Since a proportion of patients in deep molecular response (DMR: MR 4 , MR 4.5 , MR 5 ) 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 by local laboratories as well as standardized EUTOS laboratories. 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 and 2017, 3377 peripheral blood samples from 1117 CML patients were shipped to 11 standardized reference laboratories in six European countries. BCR–ABL1 transcript types were b3a2 (41.63{\%}), b2a2 (29.99{\%}), b2a2/b3a2 (3.58{\%}) and atypical (0.54{\%}). For 23.72{\%} of the 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{\%}); MR 4 , n = 685 (22.64{\%}); MR 4.5 , n = 937 (30.98{\%}); MR 5 , n = 710 (23.47{\%}). With a Cohen’s kappa coefficient of 0.708, a substantial agreement between EUTOS-certified 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.",
keywords = "BCR–ABL, Chronic myeloid leukemia, CML, Deep molecular remission, Eureka, Molecular monitoring, Standardization, TFR, Treatment-free remission",
author = "Susanne M{\"o}bius and Thomas Schenk and Danny Himsel and Jacqueline Maier and Franke, {Georg Nikolaus} and Susanne Saussele and Christiane Pott and H. Andrikovics and Nora Meggyesi and Katerina Machova-Polakova and Hana Zizkova and Tom{\'a}š Jurcek and Semir Mesanovic and Renata Zadro and Enrico Gottardi and Jens Haenig and Peter Schuld and Cross, {Nicholas C.P.} and Andreas Hochhaus and Thomas Ernst",
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T1 - Results of the European survey on the assessment of deep molecular response in chronic phase CML patients during tyrosine kinase inhibitor therapy (EUREKA registry)

AU - Möbius, Susanne

AU - Schenk, Thomas

AU - Himsel, Danny

AU - Maier, Jacqueline

AU - Franke, Georg Nikolaus

AU - Saussele, Susanne

AU - Pott, Christiane

AU - Andrikovics, H.

AU - Meggyesi, Nora

AU - Machova-Polakova, Katerina

AU - Zizkova, Hana

AU - Jurcek, Tomáš

AU - Mesanovic, Semir

AU - Zadro, Renata

AU - Gottardi, Enrico

AU - Haenig, Jens

AU - Schuld, Peter

AU - Cross, Nicholas C.P.

AU - Hochhaus, Andreas

AU - Ernst, Thomas

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 3 months during TKI treatment. Since a proportion of patients in deep molecular response (DMR: MR 4 , MR 4.5 , MR 5 ) 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 by local laboratories as well as standardized EUTOS laboratories. 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 and 2017, 3377 peripheral blood samples from 1117 CML patients were shipped to 11 standardized reference laboratories in six European countries. BCR–ABL1 transcript types were b3a2 (41.63%), b2a2 (29.99%), b2a2/b3a2 (3.58%) and atypical (0.54%). For 23.72% of the 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%); MR 4 , n = 685 (22.64%); MR 4.5 , n = 937 (30.98%); MR 5 , n = 710 (23.47%). With a Cohen’s kappa coefficient of 0.708, a substantial agreement between EUTOS-certified 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.

AB - 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 3 months during TKI treatment. Since a proportion of patients in deep molecular response (DMR: MR 4 , MR 4.5 , MR 5 ) 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 by local laboratories as well as standardized EUTOS laboratories. 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 and 2017, 3377 peripheral blood samples from 1117 CML patients were shipped to 11 standardized reference laboratories in six European countries. BCR–ABL1 transcript types were b3a2 (41.63%), b2a2 (29.99%), b2a2/b3a2 (3.58%) and atypical (0.54%). For 23.72% of the 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%); MR 4 , n = 685 (22.64%); MR 4.5 , n = 937 (30.98%); MR 5 , n = 710 (23.47%). With a Cohen’s kappa coefficient of 0.708, a substantial agreement between EUTOS-certified 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.

KW - BCR–ABL

KW - Chronic myeloid leukemia

KW - CML

KW - Deep molecular remission

KW - Eureka

KW - Molecular monitoring

KW - Standardization

KW - TFR

KW - Treatment-free remission

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