Exploring New Therapies on the Horizon for Patients With R/R Chronic Lymphocytic Leukemia

Nirav Shah, MD, Medical College of Wisconsin, Milwaukee, Wisconsin, shares insights into his research in exciting potential new therapies for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), including Bruton's tyrosine kinase (BTK) degraders and cell therapies. 

Transcript:

My name is Nirav Shah. I’m an associate professor of medicine at the Medical College of Wisconsin, and I was asked to talk about what’s new in relapsed CLL.

Here at the Medical College we are excited that we have a couple of really compelling clinical trials looking at new ways to treat patients with relapsed CLL. What’s exciting and new? There’s a new class of drugs called called BTK degraders. We first had covalent BTK inhibitors—drugs such as ibrutinib, acalabrutinib, and zanubrutinib. Recently, we have an approval of a non-covalent BTK inhibitor, a drug called pirtobrutinib.

But there’s the new generation of BTK drugs being developed called BTK degraders that go after the whole BTK enzyme, and try to degrade it. There's data that these can actually overcome resistance in those patients who have failed other BTK inhibitors. So we have a phase 1 clinical trial. There was some data presented at the EHA meeting and we hope to submit more at the ASH meeting coming up that shows preliminary efficacy and safety in heavily pretreated CLL. We look forward to developing this class of drugs, which again, may be able to overcome some of the resistance mutations that developed to current standard of care BTK inhibitors.

The good news is that the early data shows efficacy and very favorable tolerability and safety profile. So, more to come. There's more than 1 BTK degrader being developed and I think it's important that we have these different options available for those patients who have failed some of our current standard of care [therapies].

The other exciting thing that's happening in CLL is the advancement of cell therapy. Just this past year, the first CAR T-cell therapy was approved for CLL, lisocabtagene maraleucel. This is a single targeted CD19 CAR-T that showed pretty good efficacy in CLL, but a median progression-free survival of only 11 months, meaning that there is room for improvement.

Also at the Medical College here, I lead a clinical trial with dual-targeted CAR T-cells, targeting both the CD19 and CD20 protein for patients with relapsed/refractory CLL. We presented our data at the Tandem Meeting in 2024 and we had really good preliminary efficacy, with a high overall response rate. Most exciting, although with limited follow -up, all of those patients that did respond, none of them had relapsed to date. We're continuing to enroll those patients on our clinical trial and we're believers that both BTK-targeting drugs and cell therapy can be used interchangeably for patients with CLL.

Each patient with CLL has a unique story and unique presentation, and so we try to find the best treatment for each patient. Here at the medical college we're trying to advance therapies for relapsed CLL and are excited to be able to offer these trials at our centers, and many of these are offered at centers across the United States. Thank you.