Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Farhad Ravandi, Susan M O'Brien, Jorge E Cortes, Deborah M Thomas, Rebecca Garris, Stefan Faderl, Jan A Burger, Michael E Rytting, Alessandra Ferrajoli, William G Wierda, Srdan Verstovsek, Richard Champlin, Partow Kebriaei, Deborah A McCue, Xuelin Huang, Elias Jabbour, Guillermo Garcia-Manero, Zeev Estrov, Hagop M Kantarjian, Farhad Ravandi, Susan M O'Brien, Jorge E Cortes, Deborah M Thomas, Rebecca Garris, Stefan Faderl, Jan A Burger, Michael E Rytting, Alessandra Ferrajoli, William G Wierda, Srdan Verstovsek, Richard Champlin, Partow Kebriaei, Deborah A McCue, Xuelin Huang, Elias Jabbour, Guillermo Garcia-Manero, Zeev Estrov, Hagop M Kantarjian

Abstract

Background: The long-term efficacy of a combination of chemotherapy and dasatinib in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is not well established.

Methods: 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.

Results: Seventy-two patients with a median age of 55 years (range, 21-80 years) were treated; 69 (96%) achieved CR. Among them, 57 (83%) achieved cytogenetic CR after 1 cycle, and 64 (93%) achieved a major molecular response at a median of 4 weeks (range, 2-38 weeks). 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. With a median follow-up of 67 months (range, 33-97 months), 33 patients (46%) were alive, and 30 (43%) were in CR; 12 underwent allogeneic SCT. Thirty-nine patients died (3 at induction, 19 after relapse, 7 after SCT performed during first CR, and 10 during CR). The median disease-free survival and overall survival were 31 (range, 0.3-97 months) and 47 months (range, 0.2-97 months), respectively. Seven relapsed patients had BCR-ABL kinase domain mutations, including 4 with T315I.

Conclusions: A combination of chemotherapy with dasatinib is effective in achieving long-term remission for patients with newly diagnosed Ph + ALL.

Keywords: Philadelphia chromosome; acute lymphoblastic leukemia; chemotherapy; combination; dasatinib.

© 2015 American Cancer Society.

Figures

Figure 1
Figure 1
a) Disease-free survival for all patients, b) Overall survival for all patients c) Event-free survival for all patients
Figure 1
Figure 1
a) Disease-free survival for all patients, b) Overall survival for all patients c) Event-free survival for all patients
Figure 1
Figure 1
a) Disease-free survival for all patients, b) Overall survival for all patients c) Event-free survival for all patients
Figure 2
Figure 2
(a) Survival by whether or not received allogeneic stem cell transplant in CR1; (b) Survival by whether or not received transplant in CR1 and age < and ≥ 40 years
Figure 2
Figure 2
(a) Survival by whether or not received allogeneic stem cell transplant in CR1; (b) Survival by whether or not received transplant in CR1 and age < and ≥ 40 years
Figure 3
Figure 3
Grade 3 and 4 toxicities

Source: PubMed

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