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. Fiftythree 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, BCRABL levels of < 10(-3) at day 85 correlated with disease-free survival. No deaths or relapses occurred during induction. Twenty-three patients relapsed after com-pleting 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. This trial was registered at www. clinical trials. gov as # NCT00391989. (Blood. 2011; 118(25): 6521-6528)

Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia / Foa, R; Vitale, A; Vignetti, M; Meloni, G; Guarini, A; De Propris, Ms; Elia, L; Paoloni, F; Fazi, P; Cimino, G; Nobile, F; Ferrara, F; Castagnola, C; Sica, S; Leoni, P; Zuffa, E; Fozza, Claudio; Luppi, M; Candoni, A; Iacobucci, I; Soverini, S; Mandelli, F; Martinelli, G; Baccarani, M.. - In: BLOOD. - ISSN 0006-4971. - 118:25(2011), pp. 6521-6528. [10.1182/blood-2011-05-351403]

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

FOZZA, Claudio;
2011-01-01

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. Fiftythree 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, BCRABL levels of < 10(-3) at day 85 correlated with disease-free survival. No deaths or relapses occurred during induction. Twenty-three patients relapsed after com-pleting 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. This trial was registered at www. clinical trials. gov as # NCT00391989. (Blood. 2011; 118(25): 6521-6528)
2011
Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia / Foa, R; Vitale, A; Vignetti, M; Meloni, G; Guarini, A; De Propris, Ms; Elia, L; Paoloni, F; Fazi, P; Cimino, G; Nobile, F; Ferrara, F; Castagnola, C; Sica, S; Leoni, P; Zuffa, E; Fozza, Claudio; Luppi, M; Candoni, A; Iacobucci, I; Soverini, S; Mandelli, F; Martinelli, G; Baccarani, M.. - In: BLOOD. - ISSN 0006-4971. - 118:25(2011), pp. 6521-6528. [10.1182/blood-2011-05-351403]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/60340
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