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

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

Izvornik
Journal of Cancer Research and Clinical Oncology (0171-5216) 145 (2019), 6; 1645-1650

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
BCR–ABL ; CML ; chronic myeloid leukemia ; deep molecular remission ; Eureka ; molecular monitoring ; standardization ; TFR ; treatment-free remission

Sažetak
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: 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 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.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA