Experts discuss novel agents being evaluated for use as third-line treatment options and provide their closing thoughts on this discussion.
Brandon Dyson, PharmD, BCOP, BCPS: There are some newer agents on the horizon. We have vodobatinib, which is a third-generation TKI [tyrosine kinase inhibitor], similar to ponatinib. We also have olverembatinib, also a third-generation TKI. Those are both in their earlier phase trials right now. Having extra third-generation TKIs would be fantastic. They’re specifically of course getting studied in the T315I mutation, so getting extra options there is great. There’s also a newer agent called navtemadlin, which is getting looked at in CML [chronic myeloid leukemia]. Looking at clinical trials, it’s being looked in basically every hematologic malignancy and myeloproliferative setting. It might be more like throwing spaghetti at a wall and seeing what sticks, but it is getting looked at for CML as well. So we have potential options there.
We also have a couple of combination options happening. There are trials going on right now where we’re combining a TKI with lower dose interferon. Interferon plus cytarabine is what we used decades ago, before we had imatinib, before we had TKIs. It had some modest effects; tolerability was terrible. But we’ve got newer formulations of interferon alpha that make it a little easier to take now. And so, let’s look at some lower dose combinations of interferon plus a TKI. We have ruxolitinib, which is a JAK inhibitor getting looked at, in combination with a TKI. We also have asciminib, which again, binds to an allosteric site, it binds to a different part of the BCR-ABL fusion protein than our TKIs do. We’re getting that looked at with imatinib. So, what do these combinations look like? Those are the things on the horizon that could make a significant impact on what we do with our patients with CML.
Neal Dave, PharmD: CML or Ph [Philadelphia chromosome]-positive ALL [acute lymphoblastic leukemia], these are disease states in which we’ve made a lot of progress on over the last 20 years or so. I think it’s really important that we continue to focus on the patient and their specific comorbidities, their history of compliance to other therapies if you have that, and any drug interactions. We need to look at each patient individually when we’re prescribing or making guidelines, or if you’re making guidelines in your institution in this specific category. These TKIs all have slightly different adverse effects. And one that may look like it’s had a great response for a patient, or in a clinical trial, may still not be the right TKI for the patient who’s in front of you because of whatever comorbid condition they have. It’s really important, as always, to continue to look at the patient and try to fit the best therapy for them.
Transcript edited for clarity.