(Press-News.org) Researchers from 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 cord blood-derived chimeric antigen receptor (CAR) natural killer (NK) cell therapy targeting CD19.
Published today in Nature Medicine, the findings reveal 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% & 68%, respectively. The trial reported an excellent safety profile with no cases of severe cytokine release syndrome (CRS), neurotoxicity, or graft-versus-host disease.
Another key discovery of the trial was the importance of the selection criteria for allogeneic cord blood donors in CAR NK cell manufacturing. Cord blood units that were cryopreserved within 24 hours of collection and those with a low nucleated red blood cell content were associated with markedly 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, from those units with higher nucleated red blood cell content or longer collection-to-cryopreservation times.
“The responses observed in these patients are very encouraging as we continue to evaluate the long-term efficacy of CAR NK cells in the treatment of these malignancies,” said senior author Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation & Cellular Therapy. “In order to have a successful allogeneic cell therapy, it is also critical 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 yield a positive clinical response and discerned the biologic mechanisms underlying this phenomenon.”
The study also noted encouraging response rates across different types of B-cell malignancies. The OR rate at 30 days post treatment 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).
Researchers also observed durable responses with CAR NK cell treatment. One year after treatment, complete responses were seen in 83% of patients with low grade-NHL, 50% of patients with CLL and 29% of patients with DLBCL. Those with a response at 30 days post treatment were significantly more likely to have PFS at 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 stresses the importance of identifying donor-specific predictors of response after allogeneic cell therapy, especially since one donor may be used to treat hundreds of patients. CAR NK cells have the potential to be manufactured in advance and stored for off-the-shelf immediate use,” Rezvani said. “This could potentially increase patient access to these cell therapies, reduce treatment time and lower 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, extending the platform to target other antigens and malignancies, including solid tumors.
This research was supported by MD Anderson’s Moon Shots Program®, the Sally Cooper Murray Endowed Chair in Cancer Research, the National Institutes of Health (NIH) (1 R01CA211044-01, 5 P01CA148600-03, P50CA100632, CA016672), the Cancer Prevention and Research Institute of Texas (CPRIT) (RP180466) and Stand Up To Cancer. A complete list of collaborating authors and their disclosures can be found with the full paper here.
Read the full press release at the MD Anderson Newsroom.
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Disclosure
MD Anderson’s CAR NK cell therapy platform was licensed to Takeda in 2019, and MD Anderson has implemented an Institutional Conflict of Interest Management and Monitoring Plan for this research. Takeda’s investigational cryopreserved CD19-targeted CAR NK therapy (TAK-007), currently in Phase II clinical development, is of a distinct formulation from the cell therapy being developed by MD Anderson and described in this manuscript.
About MD Anderson
The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. The institution’s sole mission is to end cancer for patients and their families around the world, and, in 1971, it became one of the nation’s first National Cancer Institute (NCI)-designated comprehensive cancer centers. MD Anderson is No. 1 for cancer in U.S. News & World Report’s “Best Hospitals” rankings and has been named one of the nation’s top two hospitals for cancer since the rankings began in 1990. MD Anderson receives a cancer center support grant from the NCI of the National Institutes of Health (P30 CA016672).
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