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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4158-4164
Number of pages7
JournalCancer
Volume121
Issue number23
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

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Philadelphia Chromosome
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Drug Therapy
Stem Cell Transplantation
Therapeutics
Vincristine
Combination Drug Therapy
Dasatinib
Pericardial Effusion
Cytarabine
Residual Neoplasm
Pleural Effusion
Prednisone
Transaminases
Methotrexate
Cytogenetics
Doxorubicin
Cyclophosphamide
Dexamethasone
Disease-Free Survival

Keywords

  • acute lymphoblastic leukemia
  • chemotherapy
  • combination
  • dasatinib
  • Philadelphia chromosome

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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

In: Cancer, Vol. 121, No. 23, 01.12.2015, p. 4158-4164.

Research output: Contribution to journalArticle

Ravandi, F, O'Brien, SM, Cortes, JE, Thomas, DM, Garris, R, Faderl, S, Burger, JA, Rytting, ME, Ferrajoli, A, Wierda, WG, Verstovsek, S, Champlin, R, Kebriaei, P, Mccue, DA, Huang, X, Jabbour, E, Garcia-Manero, G, Estrov, Z & Kantarjian, HM 2015, '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', Cancer, vol. 121, no. 23, pp. 4158-4164. https://doi.org/10.1002/cncr.29646
Ravandi, Farhad ; O'Brien, Susan M. ; Cortes, Jorge E. ; Thomas, Deborah M. ; Garris, Rebecca ; Faderl, Stefan ; Burger, Jan A. ; Rytting, Michael E. ; Ferrajoli, Alessandra ; Wierda, William G. ; Verstovsek, Srdan ; Champlin, Richard ; Kebriaei, Partow ; Mccue, Deborah A. ; Huang, Xuelin ; Jabbour, Elias ; Garcia-Manero, Guillermo ; Estrov, Zeev ; Kantarjian, Hagop M. / 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. In: Cancer. 2015 ; Vol. 121, No. 23. pp. 4158-4164.
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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.",
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T1 - 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

AU - Ravandi, Farhad

AU - O'Brien, Susan M.

AU - Cortes, Jorge E.

AU - Thomas, Deborah M.

AU - Garris, Rebecca

AU - Faderl, Stefan

AU - Burger, Jan A.

AU - Rytting, Michael E.

AU - Ferrajoli, Alessandra

AU - Wierda, William G.

AU - Verstovsek, Srdan

AU - Champlin, Richard

AU - Kebriaei, Partow

AU - Mccue, Deborah A.

AU - Huang, Xuelin

AU - Jabbour, Elias

AU - Garcia-Manero, Guillermo

AU - Estrov, Zeev

AU - Kantarjian, Hagop M.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

KW - acute lymphoblastic leukemia

KW - chemotherapy

KW - combination

KW - dasatinib

KW - Philadelphia chromosome

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