Efficacy and Toxicity Considerations for Use of Ponatinib


Hagop Kantarjian, MD responds to a review of dosing options in patients with CML treated with ponatinib.


Hagop Kantarjian, MD: Let’s take the discussion in 2 parts. The first 1 is progression-free survival and survival. The follow-up is short, but the follow-up is convincing enough. At 3 years, the survival across the 3 categories is close to 90%. This may have gone unnoticed, but if you look at the experience of survival in patients who fail frontline imatinib and get on second-generation TKIs [tyrosine kinase inhibitors], their annual mortality is about 5% per year. Once you get to 5 years, the survival is 75%. With ponatinib at 3 years, the survival remains at 90%, so this is a potent drug. The annual mortality has been at 3% per year.

You emphasize the progression-free survival, but at 3 years there are enough patients to say that you can rely on the data; the curves are close. When you get to 4 years, where you’re seeing displaying the slight difference, you have only 4 patients. You can’t rely on any information beyond the third year. My interpretation is that for both survival and progression-free survival, the 3-dose schedules are equivalent. One could say, “Why are we arguing about this? The data look good, and the toxicity is less.” But if you use the 45-mg dose, you’re going to trade significant difference in toxicity because the incidence of severe arterial occlusive disease is 9.6%, and it’s halved to 5.3% if you start with 30 mg. I like this trade-off. In every patient who has T315I, I would probably take the risk of using the 45-mg dose and assume a potential risk of arterial occlusive event of 9.6%. For the other patients who don’t have the T315I mutation, the response rates are similar. The progression-free survival and survival are similar. And then the incidence of severe arterial occlusive event is only 5%.

Transcript edited for clarity.

Related Videos
Future meetings may address how immunotherapy, bispecific agents, and CAR T-cell therapies can further impact the AML treatment paradigm.
Treatment with revumenib appeared to demonstrate efficacy among patients with KMT2A-rearranged acute leukemia in the phase 2 AUGMENT-101 study.
Advocacy groups such as Cancer Support Community and the Leukemia & Lymphoma Society may help support patients with CML undergoing treatment.
Data from the REVEAL study affirm elevated white blood cell counts and higher variant allele frequency as risk factors for progression in polycythemia vera.
Additional analyses of patient-reported outcomes and MRD status in the QuANTUM-First trial are also ongoing, says Harry P. Erba, MD, PhD.
Investigators must continue to explore the space for lisocabtagene maraleucel in mantle cell lymphoma, according to Manali Kamdar, MD.
Those with CML should discuss adverse effects such as nausea or fatigue with their providers to help optimize their quality of life during treatment.
Patients with CML can become an active part of their treatment plan by discussing any questions that come to mind with their providers.
Jorge E. Cortes, MD, emphasizes proper communication between patients with chronic myeloid leukemia and their providers during the treatment course.
Dietary interventions or other medications may help mitigate diarrhea in patients who undergo therapy for chronic myeloid leukemia.
Related Content