Novel Targeted Therapies for Patients with Chronic Lymphocytic Leukemia
John Allan, MD, Weill Cornell Medicine, New York, New York, discusses updates and novel therapies, including CAR T-cell therapies, bispecific antibodies, and BTK degraders, for the treatment of chronic lymphocytic leukemia (CLL) at the 2025 Lymphoma, Leukemia & Myeloma (LL&M) Winter Symposium in Miami, Florida.
Transcript:
Hi, I am John Allan. I am a lymphoma physician in New York City at Weill Cornell. I'm here at the Winter Symposium, the LL&M Winter Symposium 2025. I was asked to give a talk on some 2024 updates in novel targeted approaches in relapsed/refractory (R/R) CLL. In that I covered various topics, CAR T-cell therapy, bispecific therapy, and a new class of drugs called BTK degraders.
We highlighted new data from the CAR T-cell therapy world, looking at combinations with ibrutinib with [lisocabtagene maraleucel] (liso-cel). Currently, liso-cel is approved as monotherapy. This cohort from the TRANSCEND NHL 001 study looked at outcomes in patients treated with ibrutinib and liso-cel.
What the investigators saw was that response rates were increased, and complete remission rates were increased. Why that's important is that with monotherapy, only 20% get to a CR. Here we're seeing close to 45% get to CR and we know those patients with a complete remission can do very, very well long-term.
We then moved on to bispecific antibodies in CLL. Epcoritamab has generated some clinical data. There were some updates at ASH of 2024. Looking at now about 30 patients treated with epcoritamab in relapsed/refractory CLL and here as a monotherapy we're seeing overall response rates of about 60+ percent and complete remission rates of around 39, 40% as well. Compares favorably to liso-cel and CAR T-cell approaches with arguably, maybe easier to use off the shelf and potentially a slightly improved toxicity profile.
There was still CRS seen in most patients, but fortunately a lot of it was low-grade, less than grade 3 cytokine release syndrome. At this update, they actually optimized the ramp-up dosing and included an extra small dose that helped mitigate the CRS and ICANS rates even further. Likely that is ongoing in development, how to best optimize and step up the dose, but nonetheless, [it was] safe, effective, and potentially an attractive option for patients in the future.
The last topic that I spoke about was BTK degraders. There are 2 that are in development in the CLL space, one with BGB-16673, and the other with NX-5948 from 2 competing industry partners. Nonetheless, while they are different molecules, they do the same thing. They degrade BTK, eliminate the scaffold function of the protein. What we have seen is that now with 50 to 60 plus patients treated in each study, response rates are excellent. They're about 70%, most are [polygenic risk scores] (PRS), but what it appears is that they remain durable, and patients continue to do phenomenally well and excitingly and expectantly.
We do see a favorable toxicity profile as well. Very few discontinuations due to adverse events. The adverse event profile is similar to what we might sometimes see with BTK inhibitors with bruising, bleeding, infections, diarrhea, cytopenias, et cetera.
Nonetheless, always low grade and very well-tolerated, and patients continue to remain benefit on study and further development in this class of drugs is ongoing and potential combinations are going to be coming forward as well. So, we look forward to that exciting data to develop.
Source:
Allan J. Updates in Bispecific Antibodies, Degraders, CAR-T Cells. Presented at Lymphoma, Leukemia & Winter Symposium; February 7-9, 2025. Miami, FL.
