Results of the European survey on the assessment of deep molecular response in chronic phase CML patients during tyrosine kinase inhibitor therapy (EUREKA registry)
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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: 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.
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.
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%); 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.
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.
KeywordsChronic myeloid leukemia CML BCR–ABL Molecular monitoring Deep molecular remission Treatment-free remission TFR Standardization Eureka
This study was funded by Novartis Oncology within the European Treatment and Outcome Study (EUTOS).
Compliance with ethical standards
Conflict of interest
All the authors declare that they have no conflict of interest.
All the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study has been approved by the ethics committee of the Jena University Hospital, Jena, Germany (No. 3944-12/12).
Informed consent was obtained from all individual participants included in the study.
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