2025 CLL Research Highlights | Dr. William Wierda

Transcript:

Jeff Folloder:  We have a discussion about evolving CLL research on deck. There have been a few research meetings since our last town hall. These include the American Society of Clinical Oncology and the European Hematology Association meetings.  Dr. Wierda, are there highlights from these meetings that you’d like to share with our viewers? 

Dr. William Wierda: Yes. Thanks, Jeff. I’m going to just very high-level introduce some of the topics that have been discussed this year. Then I think in the question session, we can get into some of the more detailed content. Over 2025, there have been several important meetings; those are summarized here. There’s the American Society of Hematology meeting. That was last December. We had our town hall after that, so we did cover content from that meeting.

Subsequently, in June, there were two important meetings: the European Hematology Association meeting and the ASCO meeting, or American Society of Clinical Oncology meeting, in June. And then, just last month, we had a large meeting in Kraków, Poland, which was the International Workshop for Chronic Lymphocytic Leukemia, which was a two-day meeting; well, actually, it was more than two days discussing various aspects of the disease and new developments and new therapies.

I made a list of sort of the hot topics for this year that have been discussed. There’s data, and there will be more data. We’re very excited and interested to see the data that’s presented at the American Society of Hematology meeting that’s coming up in December.

We’ve recently been notified of the presentations and the posters, and there’s going to be a lot of very good and interesting content, but hot topics for the year include maintenance therapy for the first-line setting; this is a BTK inhibitor-based therapy, and we’re getting long-term follow-up data from our BTK inhibitor-based treatments demonstrating very long and durable responses with continuous single-agent BTK inhibitor therapy. There’s been discussion around the choice of which BTK inhibitor.

In general, we have been directing therapy towards second-generation BTK inhibitors over ibrutinib (Imbruvica) or the first generation because of a reduced side effect and toxicity profile with those newer agents, but that is one area that’s been updated, and again, that’s the long-term exceptional outcomes that we see with continuous BTK inhibitor-based therapy.

Also, there’s been a lot of work done and published and reported recently on combination therapy. We have, for all intents and purposes, eliminated chemo, chemoimmunotherapy from our treatment strategies for our patients with CLL, both in the front-line setting and in the relapse setting, and in the front-line setting, as well as in the relapse setting, we’re working on developing combined targeted therapies, so these are oral drugs for the most part that target specific proteins. Through blocking those proteins, they will induce apoptosis and killing of the leukemia cells and put patients in remission.

And so, there are a lot of different options in terms of therapeutic agents that we have. And are combining and working on the most effective and potent combination strategy to get the highest percent of patients in remission and the highest undetectable MRD rate with our newer treatments.

And we’ve made a lot of progress. We started with venetoclax-obinutuzumab (Venclexta-Gazyva) and moved into all-oral treatment with ibrutinib plus venetoclax, acalabrutinib (Calquence) plus venetoclax. There has been some data presented with regard to sonrotoclax and zanubrutinib (Brukinsa) as an effective combination, and then we’ve reported also on our data with a triplet of pirtobrutinib (Jaypirca), venetoclax, and obinutuzumab, and again, we’re seeing very high rates of remission and undetectable MRD, and over the next five or more years, we’ll be sorting through that data and hopefully will arrive on what’s the most effective treatment in those combinations.

Pirtobrutinib: We’ve seen more data coming out on pirtobrutinib, which is referred to as a reversible BTK inhibitor. It was approved for patients who had failed a prior covalent BTK inhibitor and venetoclax, but we’re seeing that it has activity in an earlier line of treatment.

So, not necessarily restricting it to use for patients who’ve failed all prior treatments, but we’re seeing activity when it’s used earlier. Updated data on CAR T-cell therapy, and particularly CAR T cell combined with ibrutinib, and higher rates of complete remission with that combination compared to liso-cel (lisocabtagene maraleucel [Breyanzi]) or CAR T by itself.

And then there are several drugs that are in development that we’re very excited about and I think will be the next advance and wave of approvals in therapies for patients with CLL, and that’s these drugs that bind to BTK, which is an important protein in the cells that is associated with their long-term survival. These are agents that bind to that protein and induce its degradation or removal from the cells, and in removing it, the protein from the leukemia cells, that is another mechanism of killing those leukemia cells.

The inhibitors bind to that protein and block the function, but these degraders bind to that protein and completely eliminate it from the cell, which is proving to be active, and patients are tolerating these compounds in early clinical trials.

And then the bispecifics are also in development, for example, epcoritamab (Epkinly), which recruits the immune system to kill leukemia cells through engaging the immune cells of patients with CLL, T cells, for example. These agents are administered intravenously or subcutaneously, and upon doing that, they bind to the CLL cell and also bind to the T cell and induce the T cell to kill the leukemia cells. And so, that group of compounds, and particularly epcoritamab and mosunetuzumab (Lunsumio), are in development.

So, there’s a lot of exciting work. We’ve never had more progress. We’ve never had more agents available, and we’re very excited to see what we’re going to hear about at ASH this year, because it just keeps getting more and more exciting, and we see more and more promising results.