Chronic Lymphocytic Leukemia: Novel Therapies in the Pipeline


Exciting novel-based treatment strategies being investigated in chronic lymphocytic leukemia.

Susan O’Brien, MD: Just to wrap up, is there any new novel strategy or really exciting data that we haven’t covered? Maybe since you’re very familiar with it, you want to say a word about the noncovalent inhibitors. I know the pirtobrutinib data are being updated this year at ASH [American Society of Hematology annual meeting], and also we’re going to hear data, which we haven’t heard in a long time, on what used to be the ArQule drug and is now the Merck drug. I know you were leading the charge with pirtobrutinib, and maybe we can just close with a few words about I think the excitement we all have for the noncovalent inhibitors.

Anthony Mato, MD, MSCE: Sure. Yes, it’s an exciting class or an exciting potential mechanism of action in 2 drugs that are frontrunners here. The ARQ 531 molecule, which I think is now called nemtabrutinib, that’s the new name for it. Then pirtobrutinib, which was formerly LOXO-305. Interesting molecules in that they really are targeting relapsed/refractory CLL [chronic lymphocytic leukemia], particularly in patients who’ve been exposed to a prior BTK [Bruton tyrosine kinase] inhibitor and have developed the most common mechanism of resistance, which is a cysteine 481 mutation. They have a different binding mode. They bind to a different location on BTK, and the clinical data really support the fact that these drugs are active in an unmet need patient population. In terms of the LOXO-305 [pirtobrutinib] data, which I’m more familiar with, it turns out it’s a really clean BTK inhibitor in terms of its AE [adverse event] profile, a discontinuation rate of about 1% due to adverse events, which is wonderful, but not many of the classic BTK inhibitor-associated toxicities.

It’s early days, but it’s nice to have molecules that address an unmet need that happen to be well tolerated, which from a sequencing perspective can continue remissions long term for patients. The other class, which we don’t have to go over the data because there’s not a whole lot yet, is the bispecific antibodies. They seem to be really interesting and exciting, and there are some data to be presented at the ASH meeting, at least there’s a poster presentation on one of these molecules. Those are 2 really interesting classes and many other targets that are in development as well.

Susan O’Brien, MD: It’s exciting times. Well, it’s been exciting times for a while now, but it continues to be.

Anthony Mato, MD, MSCE: Yes.

Susan O’Brien, MD: Thank you, Anthony, for this really interesting conversation, and thank you, the audience. We hope you found this program informative.

Anthony Mato, MD, MSCE: Thank you so much.

Transcript edited for clarity.

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