TORNA ALL’ELENCO

Impact of BCR-ABL1 transcript type in chronic myeloid leukemia treated frontline with nilotinib in Haematologica

2017
AO Ordine Mauriziano

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (25)Vedi tutti...

Castagnetti F
Praxis Dr Grün, Bad Windsheim, Germany
Gugliotta G
Praxis Dr Grün, Bad Windsheim, Germany
Breccia M
Praxis Dr Grün, Bad Windsheim, Germany

et alii...

Abstract

Background: Chronic myeloid leukemia (CML) is driven by different transcript types, but the majority of patients have a e13a2 (b2a2) transcript, a e14a2 (b3a2) transcript or a co-expression of e13a2/e14a2 transcripts. In imatinibtreated patients, the e13a2 transcript has been associated to slower and inferior molecular responses. Few data on the prognostic impact of BCR-ABL1 transcript type in CML patients treated with second generation tyrosine kinase inhibitors (TKIs) are still available. Aims: To assess the impact of BCR-ABL1 transcript type on molecular response and outcome in newly diagnosed adult CML patients treated frontline with nilotinib (NIL). Methods: An analysis of 345 CML patients at diagnosis (chronic phase) enrolled within 3 multicentric prospective studies of the GIMEMA CML Working Party (NCT00481052, NCT00769327, NCT01535391) was performed. The initial treatment was NIL 300 mg BID or NIL 400 mg BID. Definitions: major molecular response (MMR), BCR-ABL1IS ratio <0.1%; deep molecular response (MR4.0), BCR-ABL1IS ratio <0.01% with >10,000 ABL1 copies; progression, transformation to advanced phases; death, at any time and for any reason. Cumulative incidences of response were estimated under consideration of competing risks (progression, death) and compared by Gray test. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared by log-rank test. Results: Patients expressing rare transcripts (e1a2 or e19a2; n=7) and patients with unknown transcript type (n=10) were excluded: 328 patients were evaluable, 38% with e13a2 transcript, 53% with e14a2 transcript and 9% expressing both transcripts. No significant differences in age, gender, Sokal or EUTOS long-term survival score distribution, presence of clonal chromosomal abnormalities in Ph+ cells, or NIL dose were observed. The median follow-up was 60 months (range 24-82 months). The response rates and the survival probabilities were uniformly

Keywords

BCR ABL protein; endogenous compound; nilotinib; adult; calculation; chromosome aberration; chronic myeloid leukemia; clinical trial; controlled study; death; diagnosis; DNA transcription; drug therapy; female; follow up; gender; gene expression; human; human cell; Kaplan Meier method; log rank test; long term survival; major clinical study; male; overall survival; progression free survival; prospective study; remission; stratification;