Nirav Shah, MD, on the Potential of Dual-Targeted CAR-T in Chronic Lymphocytic Leukemia

“There are lots of other groups doing dual-targeted CARS and so I think we really need to learn: What is the best next CAR-T? We're really happy with CD19-targeted CAR-T in blood cancers. It's clearly saved lives—but we can do better. So is it a CD20/CD19 CAR? Is it a CD22/CD19 CAR? Is it a combination of all of these? Lots of different groups are working on figuring out that perfect combination to really get the best outcome possible.”

LV20.19 is a bispecific CD19/CD20-targeting chimeric antigen receptor T-cell (CAR-T) therapy currently being evaluated for the treatment of patients with hematological malignancies in a phase 1/2 clinical trial (NCT04186520). Notably, the trial its treating patients with relapsed/refractory chronic lymphocytic leukemia (CLL), including patients with Richter’s transformation (RT). Results from patients with CLL and RT were recently reported in an oral presentation at the 2024 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in San Antonio, Texas, February 21-24, 2024, by principal investigator Nirav Shah, MD, an associate professor of medicine at Medical College of Wisconsin.

Following his presentation, CGTLive® sat down with Shah to talk about the results and their implications. Shah highlighted the promising efficacy findings, pointing out that the CAR-T demonstrated an overall response rate in the realm of 70% to 80%. In terms of safety, he noted that LV20.19 showed a toxicity referred to as immune effector cell hemophagocytic lymphohistiocytosis like syndrome (IEC-HS), which is unique to the CAR-T construct and primarily occurred in the patients with CLL. He stated that patients with CLL treated in the trial going forward will receive a modified dose level with the intention of ameliorating IEC-HS.

Shah also discussed how bispecific approaches to CAR-T in general may provide better outcomes than monospecific approaches to CAR-T, and as such research on bispecific CAR-T therapies will continue to be of great interest in the future. He concluded with a message to the clinical community that the trial for LV20.19 is still recruiting and may be of particular interest as it is one of the few active CAR-T trials for patients with CLL.

REFERENCES
1. Shah NN, Atallah EL, Abedin S, et al. Phase 1 trial of LV20.19 CAR T-cells for relapsed, refractory CLL and Richter’s transformation. Presented at: 2024 Tandem Meetings, February 21-24, San Antonio, Texas. Abstract #40