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 | |
| State | Published - Dec 1 2016 |
| Externally published | Yes |
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Keywords
- acute lymphoblastic leukemia
- dasatinib
- dexamethasone (hyper-CVAD [HCVAD])
- doxorubicin
- hyperfractionated cyclophosphamide
- Philadelphia chromosome
- ponatinib
- vincristine
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
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
}
TY - JOUR
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.
KW - acute lymphoblastic leukemia
KW - dasatinib
KW - dexamethasone (hyper-CVAD [HCVAD])
KW - doxorubicin
KW - hyperfractionated cyclophosphamide
KW - Philadelphia chromosome
KW - ponatinib
KW - vincristine
UR - http://www.scopus.com/inward/record.url?scp=84994427169&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994427169&partnerID=8YFLogxK
U2 - 10.1002/cncr.30231
DO - 10.1002/cncr.30231
M3 - Article
C2 - 27479888
AN - SCOPUS:84994427169
VL - 122
SP - 3650
EP - 3656
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 23
ER -