CD19-targeted CAR NK cell therapy shows promising one-year results in patients with B-cell malignancies

Researchers at the University of Texas MD Anderson Cancer Center reported promising results in a phase I/II trial of 37 patients with relapsed or refractory B-cell malignancies who were treated with antigen receptor chimeric (CAR) natural killer (NK) derived from cord blood. ) cell therapy targeting CD19.

Published in Natural medicine, results reveal an overall response rate (OR) of 48.6% 100 days after treatment, with one-year progression-free survival (PFS) and overall survival (OS) rates of 32% and 68%, respectively. The trial reported an excellent safety profile, with no cases of cytokine release syndrome (CRS), neurotoxicity, or graft-versus-host disease.

Another key finding of the trial was the importance of allogeneic cord blood donor selection criteria in the manufacturing of CAR NK cells. Cord blood units cryopreserved within 24 hours of collection and those with low nucleated red blood cell content were associated with significantly better outcomes. CAR NK cells generated from these units resulted in a one-year PFS rate of 69% and an OS rate of 94%, compared to 5% and 48%, respectively, for units with higher blood cell content. nucleated reds or a longer collection. cryopreservation times.

“The responses observed in these patients are very encouraging as we continue to evaluate the long-term effectiveness of CAR NK cells in the treatment of these malignancies,” said lead author Katy Rezvani, MD, Ph.D. , professor of stem cell transplantation. & Cellular Therapy.

“In order to have successful allogeneic cell therapy, it is also essential that we identify the characteristics of an optimal allogeneic donor for CAR NK manufacturing. We were able to identify two key factors associated with cord blood units most likely to produce a positive clinical outcome. response and discerned the biological mechanisms underlying this phenomenon.

The study also noted encouraging response rates for different types of B-cell malignancies. The CR rate 30 days after treatment was 100% in patients with low-grade non-Hodgkin’s lymphoma (NHL). , 67% in those with non-transformed chronic lymphocytic leukemia (CLL) and 41% in patients with diffuse large B-cell lymphoma (DLBCL).

Researchers also observed long-lasting responses with CAR NK cell treatment. One year after treatment, complete responses were observed in 83% of patients with low-grade NHL, 50% of patients with CLL, and 29% of patients with DLBCL. Those with a response 30 days after treatment were significantly more likely to experience PFS one year after treatment.

These results build on previous data from this trial, published in the New England Journal of Medicine, demonstrating that a single infusion of CAR NK cells achieved remission in 73% of a smaller cohort of patients with B-cell malignancies.

“Our study highlights the importance of identifying donor-specific response predictors after allogeneic cell therapy, especially since one donor can be used to treat hundreds of patients. CAR NK cells have the potential to be manufactured in advance and stored for immediate use,” Rezvani said. “This could potentially increase patient access to these cell therapies, reduce treatment duration and reduce the cost of therapy.”

The selection criteria identified in this study are being applied to select donors for ongoing and future trials at MD Anderson with engineered cord blood NK cells at MD Anderson, thereby expanding the platform to target other antigens and malignancies , including solid tumors.