EHA 2019 | CLL: two treatment paradigms

Othman Al-Sawaf

Othman Al-Sawaf, MD, University Hospital of Cologne, Cologne, Germany, discusses two treatment paradigms that have arisen in the treatment of chronic lymphocytic leukemia (CLL); ibrutinib monotherapy and fixed-duration therapy. Speaking at the 24th Congress of the European Hematology Association (EHA) 2019, held in Amsterdam, Netherlands, dr Al-Sawaf also talks on the optimization of BTK-inhibitors.

Transcript (edited for clarity):

Now with the advent of all these novel agents and combinations of novel targeted agents, we are seeing that a new treatment, two treatment paradigms have appeared. On the one hand we have seen that ibrutinib as continuous monotherapy, can achieve long and durable responses, as long as the drug is taken in. In contrast we’ve seen now that you can also have fixed-duration therapy with deep molecular responses, where the patients come off therapy and still maintain their responses as observed in CLL14 [trial].
So, for the next developments in CLL, this is really the issue; to understand whether both treatment modalities are equal with regards to efficacy. Or whether there is any advantage of one of those two regiments, with regards to tolerability, with regards to patient preference. These are the things we need to understand when we move forward, and to understand in the subsequent prospective clinical trials that have to be done.
Another challenge or another development in CLL is currently definitely, the improvement of compounds that we already have. We see a lot of clinical trials being done on alternative BTK-inhibitors. So, ibrutinib was the first in class BTK-inhibitor and now we see a broad range of other BTK-inhibitors which have been developed all aiming primarily to have better tolerability and less toxicity for the patients. For instance, we have agents like acalabrutinib, that is currently being developed and where we expect exciting new data in the next couple of months. We do see data and will see more data on zanubrutinib, also, on more specific and suggestively less toxic BTK-inhibitors.
Also, there are a number of BTK-inhibitors which are currently being developed which for instance also aim to target patients who already have BTK mutations and who should be resistant to further BTK inhibition.

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