A novel cell therapy approach using cord blood–derived natural killer (NK) cells precomplexed with the CD30/CD16A bispecific antibody AFM13 may be safe and generate responses in patients with refractory CD30-positive lymphomas, according to a recent study published by Nieto et al in Nature Medicine.
Study Methods and Results
In the phase I trial, the researchers recruited 37 adults with CD30-positive Hodgkin lymphoma and 5 patients with T-cell lymphoma who were heavily pretreated and were refractory to brentuximab vedotin and anti–PD-1 immune checkpoint inhibitors. The median age of the participants was 43 years, and they had received a median of seven prior lines of therapy.
The researchers assigned the patients to receive two to four cycles of chemotherapy followed by AFM13–NK cell infusion at three dose levels and three weekly infusions. At day 28 of each cycle, the patients’ treatment responses were evaluated, with a follow-up assessment every 3 months thereafter.
AFM13 was designed to bind to CD16A on NK cells and CD30 on lymphoma cells. Therefore, precomplexed AFM13–NK cells may be more readily able to find and eliminate CD30-positive lymphoma cells. The NK cells were first activated with cytokines, expanded in the presence of artificial antigen-presenting cells. and complexed with AFM13 prior to infusion into the patients.
Cord blood units for each cycle—used for the NK cells—were selected from The University of Texas MD Anderson Cancer Center Cord Blood Bank and chosen based on the criteria previously identified for optimal cord blood units. Donor NK cells peaked in patients’ blood 1 day after infusion, persisted up to 3 weeks, and trafficked to tumor sites.
The novel therapy demonstrated an overall response rate of 92.9% and a complete response rate of 66.7% among all trial patients. Among the patients with Hodgkin lymphoma, the overall response and complete response rates were 97.3% and 73%, respectively. At a median follow-up of 20 months, the 2-year event-free survival and overall survival rates for all participants were a respective 26.2% and 76.2%.
The median event-free survival rate was 8.8 months, and the median overall survival had not yet been reached at data cutoff. The researchers revealed that 11 of the patients remained in complete response for at least 14 months, and some of them remained in complete response up to 40 months after therapy. Further, five of the patients maintained their complete remission without any additional therapy, and six went on to receive a stem cell transplant.
The researchers reported that treatment with AFM13–NK cells was well tolerated, with no identified cases of cytokine-release syndrome, immune cell–associated neurotoxicity syndrome, or graft-vs-host disease. There was one case of a grade 2 infusion-related reaction.
Conclusions
The researchers hope the novel cell therapy may be adapted for more cancer types in future studies. “Our trial showed the favorable safety profile and encouraging activity of AFM13–NK cells in patients with heavily pretreated refractory CD30-positive Hodgkin lymphoma. We observed rapid and strong responses to this novel approach of treating patients with AFM13–NK [cells], and we continue to evaluate the efficacy of this therapy for these hard-to-treat malignancies. These data lend to this approach being considered as a possible curative treatment for some patients and a bridge to a stem cell transplant for others,” emphasized lead study author Yago Nieto, MD, PhD, Professor of Stem Cell Transplantation & Cellular Therapy at The University of Texas MD Anderson Cancer Center. “This approach, involving cytokine-induced memory cord blood–derived NK cells precomplexed with AFM13 not only holds promise for the treatment of Hodgkin lymphoma but also supports future research into the clinical applications of NK cells with bispecific engagers,” he concluded.
Disclosure: The research in this study was supported by Affimed, The University of Texas MD Anderson Cancer Center, and the National Institutes of Health. For full disclosures of the study authors, visit nature.com.
