Ponatinib is better than imatinib for frontline treatment of newly diagnosed Ph+ acute lymphoblastic leukaemia

Prof Josep Ribera - Catalan Institute of Oncology, Barcelona, Spain

The PhALLCON trial is the first and the only phase III trial that compares, directly compares, ponatinib versus imatinib combined with reduced intensity chemotherapy in newly diagnosed patients with Ph+ ALL. It’s clear that we need phase III trials and this is the only and the important clinical trial in this setting.

What was the study design?

The design of the study, it’s a randomised study, 2:1 randomisation that includes in the experimental arm ponatinib at a dose of 30mg/day and combined with vincristine and steroids after induction, methotrexate and cytarabine in consolidation and then reinductions again with vincristine and steroids and finally continuation therapy with ponatinib. The control arm is imatinib with the same chemotherapy and imatinib at the standard dose of 600mg/day.

What were the results of the study?

The primary endpoint is to assess MRD negative status at complete response if there is an improvement in the experimental arm. This main objective has been reached because MRD negative in the experimental arm is more than 30% versus less than 20% in the imatinib arm so the difference is statistically significant and this is the primary endpoint.

The secondary endpoint is event free survival. This has not been reached yet but when the first analysis has been done the follow-up is still too short to demonstrate any benefit in the experimental arm. We have to wait for a new analysis with a longer follow-up.

What is the clinical significance of these results?

This is of important clinical significance because ponatinib is the most powerful TKI inhibitor for the treatment of patients with Ph+ ALL. The importance of the results are summarised that ponatinib has been approved by the FDA with the results of this phase III study, the PhALLCON study. So in the near future we will use ponatinib as the only TKI to be combined with chemotherapy or immunotherapy for the treatment of newly diagnosed adult patients with Ph+ ALL.

What is next for this study?

Next for this study is really to demonstrate that all these initial advantages translate into a significant improvement in the event free survival. As we demonstrate in the present study to be presented at this EHA meeting, really the number of stem cell transplantations has been reduced, are reduced, in the ponatinib arm. The benefit of ponatinib is seen across all the ages and across all the subtypes, there are two subtypes of Ph+ ALL. So the advantage of ponatinib is achieved in any subtype or subgroup of Ph+ ALL. So it’s an important message and we think that we will use ponatinib