ASH 2024 | A CML Campus study assessing the transition from high-potency to low-potency inhibitors in CML

This is a work that we did together with the CML Campus, that is a group born in Italy at first with acute lymphoblastic leukemia, but then it developed also for chronic myeloid leukemia, in which all the centers and the people that work on this subject, they join in groups of subjects, thematic groups, and they can develop some ideas that they can export to the whole CML community. 

We were in the long-term group of CML and we started talking about the actual situation of CML, that your goal is to reach treatment-free remission, meaning that you stop the treatment and you don’t need to restart the treatment, hopefully, or you have to continue treatment indefinitely or at least for a very long period of time. And this is of course the main group, almost 60 to 70 percent of patients actually belong to this group, and so it’s very important to treat people without side effects or limiting the side effects that can show up after medium or long term. We are used to working in CML with a higher potency – when you change from one inhibitor to the other to go with the most potent and to the one that has less side effects. But sometimes in our clinical practice we did what is called the downgrading, meaning going from a higher potency inhibitor to a lower potency inhibitor. So to try to understand if this is something that happened only in selected centers or it was a good, not good clinical practice, but a clinical practice, we did a survey that we sent out to the centers in July asking how many patients and trying to see in those patients which were the reasons to downgrade, how was the outcome of downgrade, first in terms of eventually treatment-free remission attempt after the downgrading, and also if they did a modulation of dosage before downgrading, meaning trying to stay with the higher potency but couldn’t do that. And interestingly, the phenomenon is not limited because we harvested approximately 170 patients and of those 170 patients, approximately 30% had tried the TFR after downgrading and they succeeded, because 80% of those patients remained in TFR, even if the numbers are very limited. And also regarding the toxicities and the maintenance of the response, we saw that this is happening frequently. So this is probably a newer approach that in terms also of treatment value with the cost of the drugs increasing and the arrival of less potent generic drugs can be thought about and maybe started to be applied everywhere else too.

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