A type of novel CD NK therapy may be a promising treatment for some patients with certain blood cancers.
CD19-targeting cord blood-derived chimeric antigen receptor (CAR) natural killer (NK) cell therapy may be promising in treating patients with certain relapsed or refractory blood cancers, according to recent research published in Nature Medicine.
The phase 1/2 trial investigated a novel CAR NK therapy in 37 patients with relapsed/refractory B-cell malignancies, which include cancers such as diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL and SLL, respectively), mantle cell lymphoma and others, according to the American Cancer Society.
CAR NK Therapy Has Promising Responses, Side Effect Profile
Findings showed that 100 days after treatment, 46.8% of patients responded to therapy, meaning that their disease shrunk or disappeared. The one-year progression-free survival rate (which described the percentage of patients who are still alive and without disease progression after 12 months) was 32%, with the one-year overall survival rate (percentage of patients who are still alive, regardless of disease worsening status) at 68%.
“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,” the study’s senior author, Dr. Katy Rezvani, professor of stem cell transplantation and cellular therapy at The University of Texas MD Anderson Cancer Center, said in a press release.
Further, when the data was broken down by disease subtype, 30-day post-treatment response rates were:
- 100% in patients with low-grade non-Hodgkin lymphoma
- 67% in patients with chronic lymphocytic leukemia without transformation
- 41% in patients with DLBCL
Additionally, complete response rates (percentage of patients whose disease completely disappears) at one year were 83%, 50% and 29% in patients with low-grade non-Hodgkin lymphoma, CLL and DLBCL, respectively.
Regarding toxicity, CAR therapies carry a risk of side effects such as cytokine release syndrome (when the body releases too many inflammatory molecules, called “cytokines”), neurotoxicity (damage to the brain and other parts of the neurological system) and graft-versus-host disease (when the newly infused cells are rejected by the body). However, in this small study, the researchers did not observe any severe cases of these toxicities.
An Off-the-Shelf CAR-T Cell Therapy May Expand Access
Many CAR-T cell therapies are made by extracting a patient’s blood and reengineering their T cells to find and fight cancer. These cells are multiplied and then infused back into the patient. This process can be lengthy and expensive, according to Rezvani.
However, this CAR NK therapy is an off-the-shelf product, meaning that it is made using an unrelated donor’s cells — so in this case, cord blood — instead of the cells of the patient being treated.
“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,” Rezvani said.
Rezvani and her team discovered that cord blood units that were cryopreserved (frozen) within 24 hours of collection and those with a lower nucleated red blood cell content were associated with improved outcomes. Specifically, CAR NK cells that fit this profile led to one-year progression-free survival and overall survival rates of 69% and 94%, respectively. This was far better than the 5% and 48% progression-free survival and overall survival rates, respectively, from CAR NK cells that had a longer time to cryopreservation or higher nucleated red blood cell count.
“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.”
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