Case 1: Ponatinib in Chronic-Phase CML

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Michael J. Mauro, MD:So what if I told you that this patient was treated with ponatinib, everyone? What do we think about that?

Elias Jabbour, MD:If I have no mutations at this stage, I would consider dasatinib for this man, but if I have any mutation or have any sequencing showing any aggressive features, I would have gone to ponatinib. I’m concerned about the hypertension still, and I’ll be more on the safe side to go for dasatinib.

B. Douglas Smith, MD:It’s really interesting. Again, you get to really be a true internal medicine physician with some of these patients. They present with these comorbid illnesses. You’re looking at multiple organs that you’re helping to manage in this 62 year-old. You’re starting them on agents that can impact all of those things, and really one of the things we do is begin to minimize their risks long term. Because our expectation and our hope is that these patients will be on these drugs for not just months but years and maybe decades. And so to maximize and improve their cardiovascular risks, their risk of diabetes, and their risk related to hypertension, those all have to be really managed in patients like this. I think that came along with the patient when they walked in the door with this history, that you’re going to have to be worried about lots of other organs, not just the bone marrow.

Elias Jabbour, MD:So a question to Mike. If you want to go for ponatinib, what dose would you choose for this man?

Michael J. Mauro, MD:Let me just temper that by saying that I’m not sure I would have gone with ponatinib, but I think someone might have considered it. What dose? I think that’s an open question as well. I think we still are looking at data emerging to tell us what the right starting dose of ponatinib could be, ranging from 15 mg to 45 mg. Personally, I would have used 30 mg as an intermediate step, knowing that there may be data showing that’s a sufficient dose. Perhaps his clinician, who might have chosen ponatinib—not to say it was a bad choice—might have looked at the PACE trial where there are data for patients with only a single TKI [tyrosine kinase inhibitor] who actually did the best. But I think the devil’s in the details there, that those are really patients with imatinib exposure, generally, who had a T315I mutation. So that probably would have been the right setting for this choice, although the earlier ponatinib is used, the better the responses with regard to major and complete and durable response.

And the long-term outcomes from PACE are quite good, but we’ve all raised very important issues. In cardiovascular assessment, hypertension is a common toxicity and could very well likely get worse. I would have had a look at this patient’s cardiovascular profile probably right from the beginning, given their age and their comorbidity status and higher risk CML [chronic myeloid leukemia], knowing we might have used another therapy, and what dose to use if we were going to use it. And I think we probably might agree that this is maybe a place where ponatinib is used as a third-line therapy.

James K. McCloskey II, MD:I think we all have opportunity to discuss the dosing in further cases. But I would agree with you, I think sometimes for our patients with CML, the most important thing we might do that day is check their blood pressure and monitor their lipids because most of our patients are going to do quite well. With that in mind, I think case 2 will demonstrate the relevance of mutational testing and how that might guide our treatment decisions.

Transcript edited for clarity.