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

J 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)

MOBIUS, Susanne, Thomas SCHENK, Danny HIMSEL, Jacqueline MAIER, Georg-Nikolaus FRANKE et. al.

Basic information

Original name

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

Authors

MOBIUS, Susanne (276 Germany), Thomas SCHENK (276 Germany), Danny HIMSEL (276 Germany), Jacqueline MAIER (276 Germany), Georg-Nikolaus FRANKE (528 Netherlands), Susanne SAUSSELE (276 Germany), Christiane POTT (276 Germany), Hajnalka ANDRIKOVICS (348 Hungary), Nora MEGGYESI (348 Hungary), Katerina MACHOVA-POLAKOVA (203 Czech Republic), Hana ZIZKOVA (203 Czech Republic), Tomáš JURČEK (203 Czech Republic, belonging to the institution), Semir MESANOVIC (70 Bosnia and Herzegovina), Renata ZADRO (191 Croatia), Enrico GOTTARDI (380 Italy), Jens HAENIG (756 Switzerland), Peter SCHULD (756 Switzerland), Nicholas C. P. CROSS (826 United Kingdom of Great Britain and Northern Ireland), Andreas HOCHHAUS (276 Germany) and Thomas ERNST (276 Germany)

Edition

Journal of cancer research and clinical oncology, Springer-Verlag, 2019, 0171-5216

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.656

RIV identification code

RIV/00216224:14110/19:00111759

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1007/s00432-019-02910-6

UT WoS

000468537100023

Keywords in English

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

Abstract

V originále

PurposeThe 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 3months 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.MethodsData were collected on the standardized assessment of molecular response in the context of real-life practice. BCR-ABL1 transcript levels after>2years of TKI therapy were evaluated for DMRby 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.ResultsBetween 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%); 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 EUTOS-certified and local laboratories was shown.ConclusionsMulticenter 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.

Citovat

MOBIUS, Susanne, Thomas SCHENK, Danny HIMSEL, Jacqueline MAIER, Georg-Nikolaus FRANKE, Susanne SAUSSELE, Christiane POTT, Hajnalka ANDRIKOVICS, Nora MEGGYESI, Katerina MACHOVA-POLAKOVA, Hana ZIZKOVA, Tomáš JURČEK, Semir MESANOVIC, Renata ZADRO, Enrico GOTTARDI, Jens HAENIG, Peter SCHULD, Nicholas C. P. CROSS, Andreas HOCHHAUS and Thomas ERNST. 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. Springer-Verlag, 2019, vol. 145, No 6, p. 1645-1650. ISSN 0171-5216. Available from: https://dx.doi.org/10.1007/s00432-019-02910-6.

@article{1593317,
   author = {Mobius, Susanne and Schenk, Thomas and Himsel, Danny and Maier, Jacqueline and Franke, GeorgandNikolaus and Saussele, Susanne and Pott, Christiane and Andrikovics, Hajnalka and Meggyesi, Nora and MachovaandPolakova, Katerina and Zizkova, Hana and Jurček, Tomáš and Mesanovic, Semir and Zadro, Renata and Gottardi, Enrico and Haenig, Jens and Schuld, Peter and Cross, Nicholas C. P. and Hochhaus, Andreas and Ernst, Thomas},
   article_number = {6},
   doi = {http://dx.doi.org/10.1007/s00432-019-02910-6},
   keywords = {Chronic myeloid leukemia; CML; BCR-ABL; Molecular monitoring; Deep molecular remission; Treatment-free remission; TFR; Standardization; Eureka},
   language = {eng},
   issn = {0171-5216},
   journal = {Journal of cancer research and clinical oncology},
   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)},
   url = {http://dx.doi.org/10.1007/s00432-019-02910-6},
   volume = {145},
   year = {2019}
}

TY  - JOUR
ID  - 1593317
AU  - Mobius, Susanne - Schenk, Thomas - Himsel, Danny - Maier, Jacqueline - Franke, Georg-Nikolaus - Saussele, Susanne - Pott, Christiane - Andrikovics, Hajnalka - Meggyesi, Nora - Machova-Polakova, Katerina - Zizkova, Hana - Jurček, Tomáš - Mesanovic, Semir - Zadro, Renata - Gottardi, Enrico - Haenig, Jens - Schuld, Peter - Cross, Nicholas C. P. - Hochhaus, Andreas - Ernst, Thomas
PY  - 2019
TI  - Results of the European survey on the assessment of deep molecular response in chronic phase CML patients during tyrosine kinase inhibitor therapy (EUREKA registry)
JF  - Journal of cancer research and clinical oncology
VL  - 145
IS  - 6
SP  - 1645-1650
EP  - 1645-1650
PB  - Springer-Verlag
SN  - 01715216
KW  - Chronic myeloid leukemia
KW  - CML
KW  - BCR-ABL
KW  - Molecular monitoring
KW  - Deep molecular remission
KW  - Treatment-free remission
KW  - TFR
KW  - Standardization
KW  - Eureka
UR  - http://dx.doi.org/10.1007/s00432-019-02910-6
L2  - http://dx.doi.org/10.1007/s00432-019-02910-6
N2  - PurposeThe 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 3months 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.MethodsData were collected on the standardized assessment of molecular response in the context of real-life practice. BCR-ABL1 transcript levels after>2years of TKI therapy were evaluated for DMRby 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.ResultsBetween 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%); 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 EUTOS-certified and local laboratories was shown.ConclusionsMulticenter 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.
ER  -

MOBIUS, Susanne, Thomas SCHENK, Danny HIMSEL, Jacqueline MAIER, Georg-Nikolaus FRANKE, Susanne SAUSSELE, Christiane POTT, Hajnalka ANDRIKOVICS, Nora MEGGYESI, Katerina MACHOVA-POLAKOVA, Hana ZIZKOVA, Tomáš JURČEK, Semir MESANOVIC, Renata ZADRO, Enrico GOTTARDI, Jens HAENIG, Peter SCHULD, Nicholas C. P. CROSS, Andreas HOCHHAUS and Thomas ERNST. Results of the European survey on the assessment of deep molecular response in chronic phase CML patients during tyrosine kinase inhibitor therapy (EUREKA registry). \textit{Journal of cancer research and clinical oncology}. Springer-Verlag, 2019, vol.~145, No~6, p.~1645-1650. ISSN~0171-5216. Available from: https://dx.doi.org/10.1007/s00432-019-02910-6.

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