At the 65th Annual American Hematology Society (ASH) Meeting in San Diego, California, Nirav N Shah, MD, Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, shared expert insight into the efficacy of dual-targeted lentiviral anti-CD20/anti-CD19 (LV20.19) CAR T-cells with an adaptive manufacturing process among patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). 

Transcript:

Hi, my name is Nirav Shah. I'm an associate professor of medicine from the Medical College of Wisconsin and I'm excited to be here today at ASH 2023 to discuss my abstract titled, “A Adaptive Manufacturing of LV20.19 CAR T-Cell for Relapsed/Refractory Mantle Cell Lymphoma.”

Relapsed mantle cell lymphoma remains a disease with poor clinical outcomes. While there's been many advances with [Bruton’s tyrosine kinase] (BTK) inhibitors and [chimeric antigenm receptor] (CAR) T-cell therapies, there's still room for improvement. Our program worked on a dual-targeted bispecific CAR-T that targeted 2 proteins on B-cells: CD19 and CD20. We thought that this made sense in mantle cell lymphoma because this is biologically a disease that's actually characterized by a CD20 expression, which tends to be very high. We conducted a phase 1/2 study. This was follow-up on previous work, and what we changed was our manufacturing. 

We used more potent cytokines, and we used an adaptive manufacturing process where we would stop the manufacturing process at 8 days if the dose was met, but had the ability to extend the manufacturing to allow the cells to grow if we needed additional time. We did a phase 1 safety run-in, followed by a 14-patient phase 2 efficacy cohort. We took patients that had 2 prior lines of treatment or more and they were treated with the dual-targeted CAR 20.19 T-cells. The patient population was quite relapsed/refractory; they had a median of 4 prior lines of treatment and their average age was in their mid-60s. So, a typical mantle cell lymphoma population. [A total of] 7 of the 17 patients had a P53 aberration. We were really excited by the clinical outcomes. 

The majority of patients actually manufactured in 8 days, [and] only a few needed to extend to a 12-day process, which meant that the patients actually received CAR T-cells really, really quickly within 8 days of their apheresis. The best overall response rate for the entire population was 100%, meaning that every single patient responded. In terms of durability with a median follow-up of about 15 months, only 2 patients have relapsed. 

So far, we're very pleased with these clinical outcomes from a safety standpoint. In terms of cytokine release syndrome, we had no patient that had grade 3 to 4 cytokine release syndrome, although the majority did have lower grade cytokine release, but that's generally manageable. In terms of [immune effector cell-associated neurotoxicity syndrome] (ICANS) or neurotoxicity, we had only 2 patients with grade 3 ICANS. Both of [those were] reversible with treatment, and no patient required ICU-level care within the first 28 days. 

In conclusion, we think that this phase 1/2 study has demonstrated safety and efficacy. We think there's a really high signal here with the overall response rate, along with the fact that we've seen now durable remissions the longest. They're almost 3 years out, and so we look forward to sharing these results today at our abstract session and, actually building upon it, and hopefully starting a multi-center phase 2 study with this approach for relapsed/refractory mantle cell lymphoma.
 

Source:

Shah N, Furqan F, Szabo A, et al. Adaptive manufacturing of LV20.19 CAR t-cells for relapsed, refractory mantle cell lymphoma. Presented at the 2023 ASH Annual Meeting: December 9-12, 2023. San Diego, CA. Abstract 1024