Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia
Mené sur 53 patients atteints d'une leucémie lymphoblastique aiguë Ph+ (âge médian : 53,6 ans), cet essai évalue le dasatinib en traitement d'induction pendant 84 jours
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 >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. Post-remission 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 (OS) was 69.2% and disease-free survival (DFS) 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 to patients who never reached these levels during induction. In multivariate analysis, BCR-ABL levels of <10-3 at day +85 correlated with DFS. No deaths or relapses occurred during induction. Twenty-three patients relapsed after completing induction. A T315I mutation was detected in 12/17 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 is registered at www.clinicaltrials.gov as NCT00391989.