What is the role of dasatinib in the treatment of Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL)?

Updated: Jul 17, 2018
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

In the GIMEMA LAL1205 protocol, patients who had newly diagnosed Ph+ ALL received only dasatinib (for 84 d), steroids (for the first 32 d), and intrathecal chemotherapy as induction therapy. [50] Fifty-three patients were able to be evaluated (median age, 53.6 y). All patients achieved a complete hematologic remission; 49 patients (92.5%) achieved this at day 22. Postinduction management was decided by the investigator and included no further treatment (2 patients), tyrosine kinase inhibitor alone (19 patients), tyrosine kinase inhibitor plus chemotherapy and/or autografting (14 patients), and allografting (18 patients). At 20 months, the overall survival was 69.2% and disease-free survival was 51.1%. Twenty-three patients relapsed after completing induction.

Ravandi et al reported the long-term follow-up results of hyper-CVAD plus dasatinib for the initial treatment of patients with Ph+ ALL [51] . Patients received dasatinib with 8 cycles of alternating hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and high-dose cytarabine and methotrexate. Patients in complete remission (CR) continued maintenance dasatinib, vincristine, and prednisone for 2 years, which was followed by dasatinib indefinitely. Patients eligible for allogeneic stem cell transplantation (SCT) received it during their first CR. Seventy-two patients with a median age of 55 years were treated; 96% achieved CR. Sixty-five patients (94%) were negative for minimal residual disease assessed by flow cytometry at a median of 3 weeks (range, 2-37 weeks). Dasatinib-related grade 3 and 4 adverse events included bleeding, pleural/pericardial effusions, and elevated transaminases. The median disease-free survival and overall survival were 31 (range, 0.3-97 months) and 47 months (range, 0.2-97 months), respectively.

Rousellot et al reported a European Working Group on Adult ALL (EWALL) study of dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL [52] . Patients older than age 55 years treated with dasatinib 140 mg/day (100 mg/day over 70 years) with intrathecal chemotherapy, vincristine, and dexamethasone during induction. Patients in complete remission continued consolidation with dasatinib, sequentially with cytarabine, asparaginase, and methotrexate for 6 months. Maintenance therapy was dasatinib and vincristine/dexamethasone reinductions for 18 months followed by dasatinib until relapse or death. The complete remission rate was 96% and 65% of patients achieved a 3-log reduction in BCR-ABL1 transcript levels during consolidation. At 5 years, overall survival was 36%.


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