Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Simona Sica, R Foà, A Vitale, M Vignetti, G Meloni, A Guarini, Ms De Propris, L Elia, F Paoloni, P Fazi, G Cimino, F Nobile, F Ferrara, C Castagnola, P Leoni, E Zuffa, C Fozza, M Luppi, A Candoni, I IacobucciS Soverini, F Mandelli, G Martinelli, M. Baccarani

Risultato della ricerca: Contributo in rivistaArticolo in rivista

263 Citazioni (Scopus)

Abstract

Dasatinib is a potent BCR-ABL inhibitor effective in chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia (ALL) resistant/intolerant to imatinib. In the GIMEMA LAL1205 protocol, patients with newly diagnosed Ph(+) ALL older than 18 years (with no upper age limit) received dasatinib induction therapy for 84 days combined with steroids for the first 32 days and intrathecal chemotherapy. Postremission therapy was free. Fifty-three patients were evaluable (median age, 53.6 years). All patients achieved a complete hematologic remission (CHR), 49 (92.5%) at day 22. At this time point, 10 patients achieved a BCR-ABL reduction to < 10(-3). At 20 months, the overall survival was 69.2% and disease-free survival was 51.1%. A significant difference in DFS was observed between patients who showed at day 22 a decrease in BCR-ABL levels to < 10(-3) compared with patients who never reached these levels during induction. In multivariate analysis, BCR-ABL levels of < 10(-3) at day 85 correlated with disease-free survival. No deaths or relapses occurred during induction. Twenty-three patients relapsed after completing induction. A T315I mutation was detected in 12 of 17 relapsed cases. Treatment was well tolerated; only 4 patients discontinued therapy during the last phase of the induction when already in CHR. In adult Ph(+) ALL, induction treatment with dasatinib plus steroids is associated with a CHR in virtually all patients, irrespective of age, good compliance, no deaths, and a very rapid debulking of the neoplastic clone.
Lingua originaleEnglish
pagine (da-a)6521-6528
Numero di pagine8
RivistaBlood
Volume118
DOI
Stato di pubblicazionePubblicato - 2011

Keywords

  • Adult
  • Aged
  • Antigens, CD
  • Antineoplastic Combined Chemotherapy Protocols
  • Drug Administration Schedule
  • Female
  • Flow Cytometry
  • Fusion Proteins, bcr-abl
  • Gene Expression Regulation, Leukemic
  • Humans
  • Immunophenotyping
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Recurrence
  • Remission Induction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Steroids
  • Thiazoles
  • Time Factors
  • Treatment Outcome
  • Young Adult

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