Hyper-CVAD Plus Ponatinib May Be Effective for Newly Diagnosed Ph+ Acute Leukemia

The combination of chemotherapy with ponatinib is effective in achieving early sustained remissions in patients with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), results from an ongoing trial published online ahead of print in the journal The Lancet Oncology have shown.¹

Because the combination of chemotherapy with a tyrosine kinase inhibitor has been shown to be an effective treatment for Ph+ ALL, researchers sought to evaluate the activity and safety of combining chemotherapy with ponatinib, a more potent BCR-ABL1 inhibitor than all other tyrosine kinase inhibitors, for patients with Ph+ ALL.

For the study, researchers enrolled 37 adult patients with Ph+ ALL who had not previously received treatment or had received fewer than 2 courses of previous chemotherapy with or without tyrosine kinase inhibitors.

All participants received 8 cycles of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) alternating with high-dose methotrexate and cytarabine every 21 days. All patients also received ponatinib 45 mg daily for the first 14 days of cycle 1 then continuously during subsequent cycles.

Patients who achieved complete remission then received maintenance therapy with ponatinib 45 mg daily plus vincristine and prednisone monthly for 2 years followed by ponatinib indefinitely.

Results showed that 2-year event-free survival rate was 81% (95% CI: 64-90).

In regard to safety, the most frequent grade 3 or higher treatment-related adverse events were infections during induction, elevated aspartate aminotransferase and alanine aminotransferase concentration, thrombotic events, myocardial infarction, hypertension, rash, and pancreatitis. Three patients died potentially related to treatment.

“New strategies, including dosing titration of ponatinib and optimized control of vascular risk factors, might further improve outcomes,” the authors concluded.

Reference

1. Jabbour E, Kantarjian H, Ravandi F, et al. Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a single-centre, phase 2 study [published online ahead of print September 29, 2015]. Lancet Oncol. doi: 10.1016/S1470-2045(15)00207-7.