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Tandem Meetings 2026 | Identifying effective therapeutic approaches for patients with double-refractory CLL
Nirav Niranjan Shah, MD, Medical College of Wisconsin, Milwaukee, WI, discusses novel therapeutic approaches showing promise for patients with “double-refractory” chronic lymphocytic leukemia (CLL) who have progressed after both covalent BTK inhibitors and BCL2 inhibitors. These strategies include non-covalent BTK inhibitors, BTK degraders, and CAR T-cell therapy, all of which may represent novel options for these patients with high unmet clinical need. This interview took place virtually.
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Transcript
So, the hardest group of patients to treat in CLL are those that have progressed after both BTK inhibitors and BCL2 inhibitors. The good news for that patient population is there are new therapies available. I think of them in sort of two different classes. We have a group of drugs that can sort of reinvigorate the BTK pathway. Those are with non-covalent BTK inhibitors, drugs such as pirtobrutinib and others in clinical trials, and through another group of drugs that are currently in the clinical trial stage, of BTK degraders...
So, the hardest group of patients to treat in CLL are those that have progressed after both BTK inhibitors and BCL2 inhibitors. The good news for that patient population is there are new therapies available. I think of them in sort of two different classes. We have a group of drugs that can sort of reinvigorate the BTK pathway. Those are with non-covalent BTK inhibitors, drugs such as pirtobrutinib and others in clinical trials, and through another group of drugs that are currently in the clinical trial stage, of BTK degraders. And so these can degrade the entire BTK enzyme, and both non-covalent BTK inhibitors and BTK degraders have shown the ability to overcome resistance to covalent BTK inhibitors.
The other paradigm for this dual-exposed, dual-refractory patient population with CLL is CAR T-cell therapy, and there is a CD19 CAR-T cell therapy approved. The only limitation of that is that when you looked at the data for it, the median progression-free survival in their pivotal trial was about 12 months, and the best complete remission rate was 18%. And so it is an effective therapy, and there are people who have gotten that therapy and have gotten years of remission. So definitely something to offer patients. But part of the reason we’re continuing to investigate for new therapies is that those patients who are double-refractory definitely have the worst outcomes and are at the highest unmet clinical need for better therapeutic options. But there’s excitement on the horizon with lots of new therapies coming down the pipeline.
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