Jabbour Covers the FDA Approval of Ponatinib Plus Chemo in Ph+ ALL

Elias Jabbour, MD, a professor in the Department of Leukemia, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston, provides an overview of the significance of the FDA approval of ponatinib (Iclusig) plus chemotherapy for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

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0:09 | On March 19, the FDA granted approval for ponatinib as a first-line option for Ph+ ALL. This is the first time ever where the FDA approved a drug for first-line ALL treatment with chemotherapy. Not only [is it] the first time, but it is the first time in the history of acute leukemia where the approval was based on [minimal residual disease (MRD)] assessment at the end of induction. This is the first study in Ph+ ALL where the FDA granted approval based on meeting the primary end point of MRD-negative [complete response (CR)], and now, we have a first-line tyrosine kinase inhibitor [TKI] approved.

0:48 | The most obvious thing is you need a drug that can provide a rapid clinical benefit with an ultimate long-term improvement. There is a lot of evidence suggesting that if we can eradicate minimal disease early on, that correlates with the long-term survival benefit…There was a meta-analysis published that showed that among 13,000 patients, those who are MRD-negative did much better than [patients who were] MRD-positive and therefore, we know it does help.

1:20 | We at MD Anderson have shown that if one has 3 months [of] MRD negativity, patients have a better outcome. With this evidence, we did negotiate with the agency about considering early MRD negativity as a surrogacy for long-term outcome benefit and as such for approval. After assessing the whole evidence, the FDA agreed to consider MRD-negative CR as the primary end point. That means the patient needs to have, at the end of induction or 12 weeks, a CR sustained for a month at least, and have 10^-4 MRD negativity.