Novel CAR NK-Cell Therapy May Offer Benefit in Patients With B-Cell Malignancies
A novel chimeric antigen receptor (CAR) natural killer (NK)-cell therapy may be effective at treating patients with relapsed or refractory B-cell malignancies, according to a novel study published by Marin et al in Nature Medicine.
Study Methods and Results
In the new phase I/II trial, researchers assigned 37 patients with relapsed or refractory B-cell malignancies to receive CD19-targeted, cord blood–derived CAR NK-cell therapy. They found that the overall response rate 100 days posttreatment was 48.6% among the patients involved in the trial. The 1-year progression-free survival and overall survival rates were 32% and 68%, respectively.
The researchers also discovered the significance of the selection criteria for allogeneic cord blood donors in CAR NK-cell manufacturing. Compared with cells from units with higher nucleated red blood cell content or longer collection-cryopreservation times, CAR NK cells generated from cord blood units with a low nucleated red blood cell content that were cryopreserved within 24 hours of collection were associated with better outcomes—resulting in a 1-year progression-free survival rate of 69% vs 5% and an overall survival rate of 94% vs 48%.
“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-[cell] 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,” detailed senior study author Katy Rezvani, MD, PhD, Professor of Stem Cell Transplantation and Cellular Therapy at The University of Texas MD Anderson Cancer Center.
Additionally, the researchers noted encouraging response rates across patients with different types of B-cell malignancies. At 30 days posttreatment, the overall response rates were 100% among patients with low-grade non-Hodgkin lymphoma, 67% among those with chronic lymphocytic leukemia (CLL) without transformation, and 41% among those with diffuse large B-cell lymphoma (DLBCL). These patients were significantly more likely to experience 1-year progression-free survival. After 1-year posttreatment, the complete response rates were 83% in the patients with low-grade non-Hodgkin lymphoma, 50% in those with CLL, and 29% in those with DLBCL. None of the patients experienced severe cytokine-release syndrome, neurotoxicity, or graft-vs-host disease.
The results of the new trial built on previous findings demonstrating that a single infusion of CAR NK cells achieved remission in 73% of patients with B-cell malignancies.
“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,” highlighted Dr. Rezvani. “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. This could potentially increase patient access to these cell therapies, reduce treatment time, and lower cost of therapy,” she underscored.
The researchers concluded that the selection criteria identified in the trial are currently being applied to select donors for ongoing and future trials utilizing engineered cord blood NK cells—extending the platform to target other antigens and malignancies such as solid tumors.
Disclosure: The research in this trial was supported by The University of Texas MD Anderson Cancer Center’s Moon Shots Program, the Sally Cooper Murray Endowed Chair in Cancer Research, the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and Stand Up To Cancer. For full disclosures of the study authors, visit nature.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.