Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) plus ponatinib appears to be superior to hyper-CVAD plus dasatinib for the frontline treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), a study published in the journal Cancer has shown.1

Because the clinical efficacy of hyper-CVAD plus ponatinib has not been compared with that of hyper-CVAD plus dasatinib in this patient population in a randomized clinical trial, researchers sought to conduct a propensity score analysis to assess which targeted agent might be better with chemotherapy for first-line treatment.

For the study, investigators analyzed data from 110 patients with newly diagnosed Ph+ ALL who had participated in 2 consecutive, prospective, phase2 clinical trials that evaluated frontline hyper-CVAD with either dasatinib or ponatinib. The researchers matched 41 patients in each cohort using propensity score matching.

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Results showed that the 3-year event-free survival rate was 69% for hyper-CVAD plus ponatinib compared with 46% for hyper-CVAD plus dasatinib (P =.04); the 3-year overall survival rates were 83% and 56%, respectively (P =.03).

Using prematching cohorts, the investigators found that patients treated with hyper-CVAD plus ponatinib achieved 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.

Analyses further confirmed that treatment with hyper-CVAD plus ponatinib was associated with longer event-free survival (P =.003) and overall survival (P =.001) vs frontline therapy with hyper-CVAD and dasatinib.

Despite these findings, a randomized clinical trial is necessary to confirm these results.


1. Sasaki K, Jabbour EJ, Ravandi F, et al. 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. 2016 Aug 1. doi: 10.1002/cncr.30231. [Epub ahead of print]