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.

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.

• Authors: 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
• Journal: Cancer (Cancer) Vol. 121 Issue 23 Pg. 4158-64 (Dec 01 2015) ISSN: 1097-0142 [Electronic] United States
• PMID: 26308885 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Cancer Society.

Chemical References

• Antineoplastic Agents
• Cytarabine
• Vincristine
• Dexamethasone
• Doxorubicin
• Cyclophosphamide
• Dasatinib
• Methotrexate

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Cyclophosphamide (administration & dosage, therapeutic use)
• Cytarabine (administration & dosage, therapeutic use)
• Dasatinib (administration & dosage, therapeutic use)
• Dexamethasone (administration & dosage, therapeutic use)
• Doxorubicin (administration & dosage, therapeutic use)
• Female
• Follow-Up Studies
• Humans
• Male
• Methotrexate (administration & dosage, therapeutic use)
• Middle Aged
• Neoplasm, Residual
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, genetics)
• Survival Analysis
• Treatment Outcome
• Vincristine (administration & dosage, therapeutic use)
• Young Adult