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A groundbreaking approach in cell therapy using natural killer (NK) cells derived from cord blood, which are pre-complexed with AFM13—an innovative bispecific antibody targeting CD30 and CD16A—has shown safety and high efficacy in patients suffering from refractory CD30-positive lymphomas. This promising finding comes from a study conducted at The University of Texas MD Anderson Cancer Center.
Published in Nature Medicine, results from a Phase I trial indicated an impressive overall response rate of 92.9%, with a complete response rate of 66.7% among 42 patients who had undergone extensive prior treatments. These results highlight the potential for this specialized cell therapy to benefit certain lymphoma patients, with possibilities for adaptation to treat other cancer types in the future.
Principal investigator Yago Nieto, M.D., Ph.D., a professor of Stem Cell Transplantation & Cellular Therapy, commented on the results: “We observed rapid and robust responses to this novel treatment with AFM13-NK. Ongoing evaluations aim to further understand this therapy’s effectiveness for these challenging cancers. The data suggests the potential for this approach to serve as a curative option for some patients, as well as to act as a bridging strategy to stem cell transplantation for others.”
The innovative method utilizes Affimed’s AFM13 bispecific antibody, which facilitates binding to CD16A present on NK cells and CD30 found on lymphoma cells. This pre-complexation enhances the NK cells’ ability to identify and destroy CD30-positive lymphoma cells. The protocol involves activating NK cells with cytokines, expanding them in conjunction with synthetic antigen-presenting cells, and then complexing them with AFM13 prior to administering them to the patient.
The methodology was pioneered in the laboratory of collaborator Katy Rezvani, M.D., Ph.D., who holds the Sally Cooper Murray Endowed Chair in Cancer Research, and serves as vice president and head of MD Anderson’s Institute for Cell Therapy Discovery & Innovation. Dr. Rezvani’s team continues to innovate and refine effective cell therapies across various medical conditions.
In total, the study included 37 adults with CD30-positive Hodgkin lymphoma and five with T-cell lymphoma. These participants had previously undergone multiple treatments and had shown resistance to therapies such as brentuximab vedotin and anti-PD1 immune checkpoint inhibitors. The median age of participants stood at 43 years, and they had received an average of seven lines of prior therapy.
Patients underwent two to four cycles of chemotherapy followed by predictable AFM13-NK cell infusions, administered in three weekly doses. Responses to the treatment were assessed on the 28th day of each cycle, with further assessments occurring every three months.
The study confirmed an overall response rate (ORR) of 92.9% and a complete response (CR) of 66.7%. Particularly among patients with Hodgkin lymphoma, the ORR reached 97.3%, with a CR of 73%. After a median follow-up period of 20 months, the two-year event-free survival (EFS) and overall survival (OS) rates were reported at 26.2% and 76.2%, respectively, which is noteworthy considering the advanced state of the patients’ conditions.
The median EFS was recorded at 8.8 months, and the median OS has yet to be established at the time of data compilation—indicative of positive outcomes. Notably, eleven participants sustained complete response for a minimum of 14 months, with some experiencing this remission for as long as 40 months following the therapy. Five patients achieved complete remission without further treatment, while six others proceeded to receive stem cell transplants.
The AFM13-NK cell treatment exhibited a favorable safety profile, with no instances of cytokine release syndrome, immune cell-associated neurotoxicity syndrome, or graft-versus-host disease observed. The only recorded event was a Grade 2 infusion-related reaction.
NK cells were derived from cord blood units selected from the MD Anderson Cancer Center Cord Blood Bank based on criteria for optimal selection. Following infusion, donor NK cells peaked in the patients’ blood one day post-treatment, lasting up to three weeks and effectively localizing to tumor sites.
Dr. Nieto emphasized the significance of this trial, stating, “The favorable safety profile and promising activity of AFM13-NK cells in patients with heavily pretreated refractory CD30-positive Hodgkin lymphoma suggest this approach not only shows great promise for this particular type of lymphoma but also paves the way for future exploration into the clinical potential of combining NK cells with bispecific engagers.”
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