June 22, 2024

Promising Results in CAR NK Cell Therapy for B-Cell Malignancies

A Phase I/II trial conducted by researchers from The University of Texas MD Anderson Cancer Center has shown promising results in patients with relapsed or refractory B-cell malignancies who were treated with cord blood-derived chimeric antigen receptor (CAR) natural killer (NK) cell therapy targeting CD19. The findings, published in Nature Medicine, demonstrate an overall response (OR) rate of 48.6% at 100 days post-treatment, with one-year progression-free survival (PFS) and overall survival (OS) rates of 32% and 68% respectively. The trial also reported no cases of severe cytokine release syndrome (CRS), neurotoxicity, or graft-versus-host disease, indicating an excellent safety profile.

The study highlights the significance of donor selection criteria for allogeneic cord blood donors in CAR NK cell manufacturing. It was found that cord blood units cryopreserved within 24 hours of collection and those with low nucleated red blood cell content had significantly better outcomes. The CAR NK cells derived from these units achieved a one-year PFS rate of 69% and an OS rate of 94%, compared to 5% and 48% respectively, from units with higher nucleated red blood cell content or longer collection-to-cryopreservation times.

Senior author Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation & Cellular Therapy, expressed optimism about the responses observed in these patients and emphasized the importance of evaluating the long-term efficacy of CAR NK cells in the treatment of B-cell malignancies. Rezvani also noted the critical role of identifying optimal allogeneic donors for CAR NK manufacturing to enhance the success of allogeneic cell therapy.

The study also reported encouraging response rates across different types of B-cell malignancies. At 30 days post-treatment, the OR rate was 100% for patients with low-grade non-Hodgkin lymphoma (NHL), 67% for those with chronic lymphocytic leukemia (CLL) without transformation, and 41% in patients with diffuse large B-cell lymphoma (DLBCL). Additionally, durable responses were observed with CAR NK cell treatment, with 83% of patients with low-grade NHL, 50% of patients with CLL, and 29% of patients with DLBCL achieving complete responses one year after treatment. Patients with a response at 30 days post-treatment were significantly more likely to have PFS at one year.

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

Rezvani highlighted the importance of identifying donor-specific predictors of response after allogeneic cell therapy, particularly since one donor may be used to treat multiple patients. CAR NK cells have the potential to be manufactured in advance and stored for off-the-shelf immediate use, which could increase patient access to these cell therapies, reduce treatment time, and lower the cost of therapy.

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

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