1. Results of the European survey on the assessment of deep molecular response in chronic phase CML patients during tyrosine kinase inhibitor therapy (EUREKA registry).
- Author
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Möbius, Susanne, Schenk, Thomas, Himsel, Danny, Maier, Jacqueline, Franke, Georg-Nikolaus, Saussele, Susanne, Pott, Christiane, Andrikovics, Hajnalka, 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, and Ernst, Thomas
- Subjects
PROTEIN-tyrosine kinases ,CHRONIC myeloid leukemia ,KINASE inhibitors - 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 , 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 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%); 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. 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. [ABSTRACT FROM AUTHOR]- Published
- 2019
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