CML Management: Personal Experience With Asciminib


Experts share their personal experience with asciminib as later-line therapy for patients with chronic myeloid leukemia.


Moshe Talpaz, MD: My experience with asciminib is often very gratifying. I treated about 15 patients with asciminib during the phase 1 study, and it was an interesting mix. The most impressive fighter element was patients with very long-standing disease who’ve never achieved any type of cytogenetic or molecular remission. To our surprise, some of these patients achieved major or even complete molecular response. At this point, I can count at least 5 patients with major molecular response or complete response, something they’ve never seen with any other therapy prior to the use of asciminib. When we say any other therapy, some of the patients were also treated with ponatinib and did not have a response beyond hematologic response. That was another very rewarding response, and very gratifying.

Daniel J. DeAngelo, MD, PhD: My experience with asciminib has been derived solely by clinical trial participation. We participated in the phase 1 and 3 and are now on the expanded-access protocols for patients. Our patients had been previously treated with multiple tyrosine kinases, sometimes exhausting all the available ones. There are 2 groups of patients I’ve treated. There are those patients who were intolerant. Remember, all the other approved kinase inhibitors are ATP mimetic, and they have different toxicities. There are some overlapping similarities among the ATP-mimetic agents, which are different from asciminib. You have a patient who’s intolerant to 2 or more, and then they hit or receive asciminib. They seem to respond to or at least tolerate it better. That’s 1 observation.

The other group of patients I’ve treated on these various trials are those who aren’t just intolerant but resistant to 2 or more prior tyrosine kinase inhibitors [TKIs]. In those patients, through a different mechanism of action, asciminib is able to recapture some of the activity and therefore place a patient into a good disease state with the goal of achieving a 3-log reduction or major molecular response, MMR. Those are the 2 major groups of patients, those that are intolerant, and those who have a suboptimal refractory response to prior TKI therapy. Asciminib seems to fill the hole for both of those groups of patients.

Jorge E. Cortes, MD: I’ve been fortunate to be able to use asciminib from the very early phase 1 study and recently even with the commercial drug. In both the settings of the patients who have received multiple prior TKIs, as well as in patients with T359. My experience matches what we’ve seen in the clinical trials, meaning I’ve seen very good levels of response. Most of my patients have responded and also have these very good safety profiles. Patients tolerate the drug very well.

One concern for asciminib has been that you have to do it with nothing to eat 2 hours prior and 1 hour after. But if you help the patient understand how this can be done, this is easily manageable for most patients. For example, the dosage can be 40 mg twice daily or 80 mg once daily. Many patients will prefer the once daily, and that helps. And for the 2 hours prior, I mentioned to the patients, for example, that if you take it first thing in the morning, because you’ll be fasting while asleep, that takes care of the 2 hours prior. Then you just have to kill an hour before you eat breakfast, by the time you get ready, etc. If you can guide your patient and find ways to manage these, most find it very manageable. Because the toxicity profile is good then very quickly they become comfortable with doing this.

You need to monitor. It’s important to monitor the blood counts, the CBC [complete blood count]. When patients move to later lines of therapy, they’re more likely to have thrombocytopenia and some neutropenia. You want to monitor that, stop therapy if it’s grade 3 or greater, and resume when it resolves. Monitoring the lipids as well is important. If it gets to be grade 3 or higher, then I stop and monitor the patients. Once it resolves, resume with some dose adjustments. Assess if the patient has clinical pancreatitis. Most of the time that’s not the case, but it’s important to keep an eye, and of course we do the assessment of all other comorbidities and other conditions the patient may have.

Transcript edited for clarity.

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