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EHA 2026 | Dual-targeted CD19/CD20 CAR-T shows promising efficacy in relapsed/refractory CLL
Nirav Niranjan Shah, MD, Medical College of Wisconsin, Milwaukee, WI, discusses findings from the Phase I LV20.19 study (NCT04186520) of a dual-targeted anti-CD20/anti-CD19 CAR-T cell therapy in relapsed/refractory chronic lymphocytic leukemia (CLL). He highlights the rationale for dual-antigen targeting, key safety observations that led to dose optimization, and the encouraging efficacy results, including high response rates and promising progression-free survival (PFS). This interview took place at the 31st Congress of the European Hematology Association (EHA) in Stockholm, Sweden.
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Transcript
We know that CAR T-cell therapy is an important treatment for patients with relapsed/refractory CLL. There’s one FDA-approved product called lysacaptogene, and with that product, at least in their pivotal clinical trial, we had a median progression-free survival of about 12 months. So what that tells us is that this is an effective single infusion therapy, but about a year later, half the patients have either relapsed or died or had an event leading to that outcome...
We know that CAR T-cell therapy is an important treatment for patients with relapsed/refractory CLL. There’s one FDA-approved product called lysacaptogene, and with that product, at least in their pivotal clinical trial, we had a median progression-free survival of about 12 months. So what that tells us is that this is an effective single infusion therapy, but about a year later, half the patients have either relapsed or died or had an event leading to that outcome. And so the question is, can we do better? And so one of the ways to make CAR T-cells more effective is to target more than one B cell antigen. We know that in CLL in particular, that this is a disease very sensitive to CD20 targeting. In fact, obinutuzumab is the mainstay of a lot of different treatments for CLL. And so we had a hypothesis of targeting both 19, a known target for CAR-T, and 20, a known target in CLL, that a dual-targeted construct could potentially improve the efficacy. And so we launched a phase one clinical trial using the LV20.19 construct for patients with relapsed refractory CLL. With that trial, we looked at both the safety and efficacy of this construct. And so first with the safety, we did see that there was a different signal in the CLL patients. At the standard dose we use in other B cell malignancies of two and a half million cells per kilo, we actually found that in CLL patients, we were seeing high rates of ICANS, so immunocyte-activated cell neurotoxicity syndrome, and actually had some patients have poor outcomes as a result of that. So we actually modified the clinical trial and dropped the dose to one million by 10 to the 6 cells per kilo. And after doing that, we actually got a better safety and efficacy signal. For the overall population, though, including both dose levels, we have an overall response rate of 90% and a CR rate of 80% and a two-year progression-free survival of 77%. And so we haven’t actually reached the median progression-free survival on this clinical trial to date. And so very early data, phase one, you know, a small number of patients, but we’re seeing a signal that dual targeting may improve the efficacy of CAR T-cell therapy in patients with relapsed refractory CLL. We hope this data will sort of be encouraging to do further studies with this construct or any studies that involve targeting more than one B-cell antigen.
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