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Published on December 29, 2020
Clinical Trials Bring New Treatment Options for CML
Exciting news for CML patients was presented at this year's American Society of Hematology (ASH) conference. In this segment, host and Patient Power co-founder Andrew Schorr is joined by Michael Deininger, MD, PhD, of University of Utah's Huntsman Cancer Institute to discuss what has been learned from several recent clinical trials for chronic myelogenous leukemia.
The ASCEMBL Phase Three Trial reports new treatment options for CML patients who have not had successful results with prior tyrosine-kinase inhibitors (TKIs). The OPTIC trial studied dosing regimens for the tyrosine-kinase inhibitor ponatinib (Iclusig). Watch here to learn more.
Transcript | New Treatment Options for Chronic Myelogenous Leukemia
Andrew Schorr: Hello, and welcome to Patient Power. I'm Andrew Schorr in California, and joining us from Utah is an old friend, Dr. Michael Deininger. Dr. Deininger is the Chief of Hematology and Hematologic Malignancies at the Huntsman Cancer Institute in the University of Utah. Dr. Deininger, welcome back to Patient Power.
Dr. Deininger: Thank you.
Andrew Schorr: Dr. Deininger, so we've talked over the years about CML, we've just had the American Society of Hematology meeting virtually and CML is discussed. Are there any developments there that you would want to call out as significant for people newly diagnosed or living with CML?
What is the Latest News from Chronic Myelogenous Leukemia Clinical Trials?
Dr. Deininger: Yeah, I think there are a couple of exciting clinical studies that have been reported. So, one is the so-called ASCEMBL trial that is a study that compared the new tyrosine kinase inhibitor asciminib versus bosutinib (Bosulif) in patients who had failed prior to TKIs. So that study is a randomized comparison and it read out positive for asciminib, in terms of molecular response at six months. So, this is quite exciting because it really adds another compound or hopefully will add another compound and another agent to the CML armamentarium. So asciminib has activity against most of the BCR-ABL1 mutants that confer resistance to variants of the approved TKIs. And at higher dose, that also includes the T315I mutation. Actually, there was another report specifically on T315I, and again, this showed very promising results. So, I think this is really a glimmer of hope.
The third study that is significant is related to ponatinib or Iclusig. So many patients will of course know about that, this is the third-generation inhibitor that is being used mainly in patients who fail imatinib (Gleevec), and other second-generation inhibitors, such as dasatinib (Sprycel) and has activity against the T315I mutation. Now as many of you will remember, ponatinib got a lot of bad press, if you will, because it became clear that it has significant cardiovascular toxicity. So blood clots and strokes, heart attacks. And so, this trial that was reported is called the OPTIC trial that compared 3 different doses of ponatinib to see whether you can find a sweet spot, that doesn't cause as much toxicity, but still maintains efficacy. And it seems that the highest dose of ponatinib in that study is the 45-milligram dose that is currently the FDA approved dose does cause cardiovascular toxicity, but it is certainly less than expected from previous work.
And most patients treated at this high dose who were then reduced in their dose, were able to maintain their responses. So, it's a bit of a complicated study, but maybe suffice it to say that it really allows us to be a little bit more confident in our dose selections for ponatinib and in a way, somewhat redraw the therapeutic space by using lower doses or deescalating the dose at an early time point. So, this is an important study as well.
Andrew Schorr: Okay. So it sounds like tweaking. So many people do well in their treatment with CML tweaking the doses, seeing how different lines of therapies can work. But I think the story still remains very positive, doesn't it?
What Should CML Patients Know About Today’s Treatment Options?
Dr. Deininger: All in all, if you look at CML, it's just an incredible story. It really is from 25 years ago to where we are now, this is just unbelievable. We are very privileged to have all these agents available and to find something for hopefully almost every patient to give them a good quality of life and a normal survival. Sometimes it's about optimizing the use of the tool you have already available that can make additional differences or an additional difference.
Andrew Schorr: Dr. Michael Deininger from the University of Utah Huntsman Cancer Institute. Thank you for being with us today and explaining all these updates.
Dr. Deininger: You're very welcome and have a good day to everyone.
Andrew Schorr: Thank you. I'm Andrew Schorr. Remember knowledge can be the best medicine of all.
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