Hagop KantarjianLeukemia research and cancer drug policy

Ponatinib for CML and Ph+ ALL: five-year results from the PACE trial

12 Oct 2023 · 1 min

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1:16

In this presentation, the speaker highlights the significance of the five‑year data from the PACE trial for ponatinib, a third‑generation tyrosine‑kinase inhibitor used in chronic myeloid leukemia (CML) and Philadelphia‑positive acute lymphoblastic leukemia (Ph+ ALL). The trial confirms ponatinib’s high efficacy, showing a major molecular response (MMR) rate of about 40% in the study (up to ~70% in real‑world settings) and an estimated five‑year overall survival of roughly 75% in patients who have failed two prior TKIs. However, the drug is also associated with notable toxicity and high cost. Importantly, the data demonstrate that the standard 45 mg daily dose is unnecessary for most patients; a regimen of 30 mg daily, reduced to 15 mg once a PCR level falls below 1%, is sufficient, with the higher dose reserved for T315I‑mutated disease. This dose reduction maintains efficacy while potentially lowering toxicity and expense.

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So the PACE is very important data for 2 reasons. We know that ponatinib is a highly effective 3rd-generation TKI, and actually in patients who have failed 2 TKIs, ponatinib has given outstanding results with a major molecular response rate, which was reported to be 40%, but in the real-world data, it's up to about 70%. And then the estimated 5-year survival is an incredible rate of about 75%. So ponatinib is a very effective drug, but it's also a toxic drug and it's quite expensive. So the 5-year PACE data has shown that you really don't need to use ponatinib at 45 milligrams daily in most of the instances except for T315I mutated disease. You can use it at 30 milligrams daily and reduce then to 15 milligrams daily once the patients achieve a PCR less than 1%. So the PACE data confirms that ponatinib is not only highly effective, it can be used at a lower dose, which is less toxic also.