Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A propensity score analysis

Koji Sasaki; Elias J. Jabbour; Farhad Ravandi; Nicholas J. Short; Deborah A. Thomas; Guillermo Garcia-Manero; Naval G. Daver; Tapan M. Kadia; Marina Y. Konopleva; Nitin Jain; Ghayas C. Issa; Vicki Jeanis; Haim G. Moore; Rebecca S. Garris; Naveen Pemmaraju; Jorge E. Cortes; Susan M. O'Brien; Hagop M. Kantarjian

doi:10.1002/cncr.30231

Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A propensity score analysis

Koji Sasaki, Elias J. Jabbour, Farhad Ravandi, Nicholas J. Short, Deborah A. Thomas, Guillermo Garcia-Manero, Naval G. Daver, Tapan M. Kadia, Marina Y. Konopleva, Nitin Jain, Ghayas C. Issa, Vicki Jeanis, Haim G. Moore, Rebecca S. Garris, Naveen Pemmaraju, Jorge E. Cortes, Susan M. O'Brien, Hagop M. Kantarjian

Research output: Contribution to journal › Article › peer-review

79 Scopus citations

Abstract

BACKGROUND: The clinical efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD) plus ponatinib has not been compared with that of HCVAD plus dasatinib in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in a randomized clinical trial. METHODS: The authors analyzed 110 patients with newly diagnosed Ph+ ALL who were enrolled in 2 consecutive, prospective, phase 2 clinical trials of frontline HCVAD with either dasatinib (63 patients) or ponatinib (47 patients). Propensity score analysis with 1:1 matching with the nearest neighbor matching method and inverse probability of treatment weighting (IPTW) analysis based on the propensity scores were performed to assess response rates, event-free survival (EFS), and overall survival (OS) between the cohorts. RESULTS: Propensity score matching identified 41 patients in each cohort. With propensity score matching, the 3-year EFS rates for patients treated with HCVAD plus ponatinib and HCVAD plus dasatinib were 69% and 46%, respectively (P =.04), and the 3-year OS rates were 83% and 56%, respectively (P =.03). IPTW analysis using prematching cohorts demonstrated that patients treated with HCVAD plus ponatinib had significantly higher rates of minimal residual disease negativity by flow cytometry on day 21, complete cytogenetic response at complete response, major molecular response at complete response and at 3 months, and complete molecular response at 3 months. IPTW confirmed that treatment with HCVAD plus ponatinib was associated with longer EFS (P =.003) and OS (P =.001) compared with treatment with HCVAD plus dasatinib. CONCLUSIONS: The clinical outcome of patients treated with HCVAD plus ponatinib appears to be superior to that of patients treated with HCVAD plus dasatinib among individuals with Ph+ ALL. Cancer 2016;122:3650-6.

Original language	English (US)
Pages (from-to)	3650-3656
Number of pages	7
Journal	Cancer
Volume	122
Issue number	23
DOIs	https://doi.org/10.1002/cncr.30231
State	Published - Dec 1 2016
Externally published	Yes

Keywords

Philadelphia chromosome
acute lymphoblastic leukemia
dasatinib
dexamethasone (hyper-CVAD [HCVAD])
doxorubicin
hyperfractionated cyclophosphamide
ponatinib
vincristine

ASJC Scopus subject areas

Oncology
Cancer Research

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Sasaki, K., Jabbour, E. J., Ravandi, F., Short, N. J., Thomas, D. A., Garcia-Manero, G., Daver, N. G., Kadia, T. M., Konopleva, M. Y., Jain, N., Issa, G. C., Jeanis, V., Moore, H. G., Garris, R. S., Pemmaraju, N., Cortes, J. E., O'Brien, S. M., & Kantarjian, H. M. (2016). Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A propensity score analysis. Cancer, 122(23), 3650-3656. https://doi.org/10.1002/cncr.30231

Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia : A propensity score analysis. / Sasaki, Koji; Jabbour, Elias J.; Ravandi, Farhad; Short, Nicholas J.; Thomas, Deborah A.; Garcia-Manero, Guillermo; Daver, Naval G.; Kadia, Tapan M.; Konopleva, Marina Y.; Jain, Nitin; Issa, Ghayas C.; Jeanis, Vicki; Moore, Haim G.; Garris, Rebecca S.; Pemmaraju, Naveen; Cortes, Jorge E.; O'Brien, Susan M.; Kantarjian, Hagop M.

In: Cancer, Vol. 122, No. 23, 01.12.2016, p. 3650-3656.

Research output: Contribution to journal › Article › peer-review

Sasaki, K, Jabbour, EJ, Ravandi, F, Short, NJ, Thomas, DA, Garcia-Manero, G, Daver, NG, Kadia, TM, Konopleva, MY, Jain, N, Issa, GC, Jeanis, V, Moore, HG, Garris, RS, Pemmaraju, N, Cortes, JE, O'Brien, SM & Kantarjian, HM 2016, 'Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A propensity score analysis', Cancer, vol. 122, no. 23, pp. 3650-3656. https://doi.org/10.1002/cncr.30231

Sasaki, Koji ; Jabbour, Elias J. ; Ravandi, Farhad ; Short, Nicholas J. ; Thomas, Deborah A. ; Garcia-Manero, Guillermo ; Daver, Naval G. ; Kadia, Tapan M. ; Konopleva, Marina Y. ; Jain, Nitin ; Issa, Ghayas C. ; Jeanis, Vicki ; Moore, Haim G. ; Garris, Rebecca S. ; Pemmaraju, Naveen ; Cortes, Jorge E. ; O'Brien, Susan M. ; Kantarjian, Hagop M. / Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia : A propensity score analysis. In: Cancer. 2016 ; Vol. 122, No. 23. pp. 3650-3656.

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title = "Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A propensity score analysis",

abstract = "BACKGROUND: The clinical efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD) plus ponatinib has not been compared with that of HCVAD plus dasatinib in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in a randomized clinical trial. METHODS: The authors analyzed 110 patients with newly diagnosed Ph+ ALL who were enrolled in 2 consecutive, prospective, phase 2 clinical trials of frontline HCVAD with either dasatinib (63 patients) or ponatinib (47 patients). Propensity score analysis with 1:1 matching with the nearest neighbor matching method and inverse probability of treatment weighting (IPTW) analysis based on the propensity scores were performed to assess response rates, event-free survival (EFS), and overall survival (OS) between the cohorts. RESULTS: Propensity score matching identified 41 patients in each cohort. With propensity score matching, the 3-year EFS rates for patients treated with HCVAD plus ponatinib and HCVAD plus dasatinib were 69% and 46%, respectively (P =.04), and the 3-year OS rates were 83% and 56%, respectively (P =.03). IPTW analysis using prematching cohorts demonstrated that patients treated with HCVAD plus ponatinib had significantly higher rates of minimal residual disease negativity by flow cytometry on day 21, complete cytogenetic response at complete response, major molecular response at complete response and at 3 months, and complete molecular response at 3 months. IPTW confirmed that treatment with HCVAD plus ponatinib was associated with longer EFS (P =.003) and OS (P =.001) compared with treatment with HCVAD plus dasatinib. CONCLUSIONS: The clinical outcome of patients treated with HCVAD plus ponatinib appears to be superior to that of patients treated with HCVAD plus dasatinib among individuals with Ph+ ALL. Cancer 2016;122:3650-6.",

keywords = "Philadelphia chromosome, acute lymphoblastic leukemia, dasatinib, dexamethasone (hyper-CVAD [HCVAD]), doxorubicin, hyperfractionated cyclophosphamide, ponatinib, vincristine",

author = "Koji Sasaki and Jabbour, {Elias J.} and Farhad Ravandi and Short, {Nicholas J.} and Thomas, {Deborah A.} and Guillermo Garcia-Manero and Daver, {Naval G.} and Kadia, {Tapan M.} and Konopleva, {Marina Y.} and Nitin Jain and Issa, {Ghayas C.} and Vicki Jeanis and Moore, {Haim G.} and Garris, {Rebecca S.} and Naveen Pemmaraju and Cortes, {Jorge E.} and O'Brien, {Susan M.} and Kantarjian, {Hagop M.}",

note = "Publisher Copyright: {\textcopyright} 2016 American Cancer Society",

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doi = "10.1002/cncr.30231",

language = "English (US)",

volume = "122",

pages = "3650--3656",

journal = "Cancer",

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T1 - Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

T2 - A propensity score analysis

AU - Sasaki, Koji

AU - Jabbour, Elias J.

AU - Ravandi, Farhad

AU - Short, Nicholas J.

AU - Thomas, Deborah A.

AU - Garcia-Manero, Guillermo

AU - Daver, Naval G.

AU - Kadia, Tapan M.

AU - Konopleva, Marina Y.

AU - Jain, Nitin

AU - Issa, Ghayas C.

AU - Jeanis, Vicki

AU - Moore, Haim G.

AU - Garris, Rebecca S.

AU - Pemmaraju, Naveen

AU - Cortes, Jorge E.

AU - O'Brien, Susan M.

AU - Kantarjian, Hagop M.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - BACKGROUND: The clinical efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD) plus ponatinib has not been compared with that of HCVAD plus dasatinib in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in a randomized clinical trial. METHODS: The authors analyzed 110 patients with newly diagnosed Ph+ ALL who were enrolled in 2 consecutive, prospective, phase 2 clinical trials of frontline HCVAD with either dasatinib (63 patients) or ponatinib (47 patients). Propensity score analysis with 1:1 matching with the nearest neighbor matching method and inverse probability of treatment weighting (IPTW) analysis based on the propensity scores were performed to assess response rates, event-free survival (EFS), and overall survival (OS) between the cohorts. RESULTS: Propensity score matching identified 41 patients in each cohort. With propensity score matching, the 3-year EFS rates for patients treated with HCVAD plus ponatinib and HCVAD plus dasatinib were 69% and 46%, respectively (P =.04), and the 3-year OS rates were 83% and 56%, respectively (P =.03). IPTW analysis using prematching cohorts demonstrated that patients treated with HCVAD plus ponatinib had significantly higher rates of minimal residual disease negativity by flow cytometry on day 21, complete cytogenetic response at complete response, major molecular response at complete response and at 3 months, and complete molecular response at 3 months. IPTW confirmed that treatment with HCVAD plus ponatinib was associated with longer EFS (P =.003) and OS (P =.001) compared with treatment with HCVAD plus dasatinib. CONCLUSIONS: The clinical outcome of patients treated with HCVAD plus ponatinib appears to be superior to that of patients treated with HCVAD plus dasatinib among individuals with Ph+ ALL. Cancer 2016;122:3650-6.

AB - BACKGROUND: The clinical efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD) plus ponatinib has not been compared with that of HCVAD plus dasatinib in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in a randomized clinical trial. METHODS: The authors analyzed 110 patients with newly diagnosed Ph+ ALL who were enrolled in 2 consecutive, prospective, phase 2 clinical trials of frontline HCVAD with either dasatinib (63 patients) or ponatinib (47 patients). Propensity score analysis with 1:1 matching with the nearest neighbor matching method and inverse probability of treatment weighting (IPTW) analysis based on the propensity scores were performed to assess response rates, event-free survival (EFS), and overall survival (OS) between the cohorts. RESULTS: Propensity score matching identified 41 patients in each cohort. With propensity score matching, the 3-year EFS rates for patients treated with HCVAD plus ponatinib and HCVAD plus dasatinib were 69% and 46%, respectively (P =.04), and the 3-year OS rates were 83% and 56%, respectively (P =.03). IPTW analysis using prematching cohorts demonstrated that patients treated with HCVAD plus ponatinib had significantly higher rates of minimal residual disease negativity by flow cytometry on day 21, complete cytogenetic response at complete response, major molecular response at complete response and at 3 months, and complete molecular response at 3 months. IPTW confirmed that treatment with HCVAD plus ponatinib was associated with longer EFS (P =.003) and OS (P =.001) compared with treatment with HCVAD plus dasatinib. CONCLUSIONS: The clinical outcome of patients treated with HCVAD plus ponatinib appears to be superior to that of patients treated with HCVAD plus dasatinib among individuals with Ph+ ALL. Cancer 2016;122:3650-6.

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KW - acute lymphoblastic leukemia

KW - dasatinib

KW - dexamethasone (hyper-CVAD [HCVAD])

KW - doxorubicin

KW - hyperfractionated cyclophosphamide

KW - ponatinib

KW - vincristine

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Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A propensity score analysis

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Keywords

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