A novel cell therapy combining cord blood-derived natural killer (NK) cells with a bispecific antibody has demonstrated remarkable efficacy in patients with refractory CD30-positive lymphomas, according to new research from The University of Texas MD Anderson Cancer Center.
The Phase I trial results, published in Nature Medicine, revealed an impressive 92.9% overall response rate and 66.7% complete response rate among 42 heavily pretreated patients. These findings suggest significant potential for this innovative approach in treating specific lymphoma patients and possibly other cancer types in the future.
"We observed rapid and strong responses to this novel approach of treating patients with AFM13-NK, and we continue to evaluate the efficacy of this therapy for these hard-to-treat malignancies," said principal investigator Yago Nieto, M.D., Ph.D., professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson. "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."
Innovative Mechanism of Action
The trial's approach utilizes Affimed's AFM13 (acimtamig) bispecific antibody, specifically designed to bind simultaneously to CD16A receptors on NK cells and CD30 on lymphoma cells. This dual-binding mechanism enables the pre-complexed AFM13-NK cells to more effectively target and eliminate CD30-positive lymphoma cells.
The preparation process involves several key steps: NK cells are first activated with cytokines, then expanded in the presence of artificial antigen-presenting cells, and finally complexed with AFM13 before patient infusion.
This technique originated in the laboratory of Dr. Katy Rezvani, Sally Cooper Murray Endowed Chair in Cancer Research and vice president of MD Anderson's Institute for Cell Therapy Discovery & Innovation, who continues to develop advanced cell therapies for various conditions.
Trial Design and Patient Population
The study enrolled a challenging patient population consisting of 37 adults with CD30-positive Hodgkin lymphoma and five with T-cell lymphoma. All participants had previously failed treatment with brentuximab vedotin and anti-PD1 immune checkpoint inhibitors, with a median of seven prior therapy lines. The median age of participants was 43 years.
Treatment protocol involved two to four cycles of chemotherapy followed by AFM13-NK cell infusion at three dose levels with three weekly infusions. Response evaluation occurred at day 28 of each cycle, with follow-up assessments every three months thereafter.
Impressive Efficacy Results
The therapy demonstrated exceptional efficacy, particularly in Hodgkin lymphoma patients who achieved a 97.3% overall response rate and 73% complete response rate. For the entire cohort, at a median follow-up of 20 months, the two-year event-free survival (EFS) and overall survival (OS) rates were 26.2% and 76.2%, respectively—notable results given the heavily pretreated and refractory nature of the patients' disease.
The median EFS was 8.8 months, while median OS had not yet been reached at data cutoff, indicating promising durability. Eleven patients maintained complete responses for at least 14 months, with some extending to 40 months post-therapy. Five patients sustained complete remission without additional therapy, while six proceeded to stem cell transplantation.
Favorable Safety Profile
The AFM13-NK cell treatment demonstrated excellent tolerability with no cases of cytokine release syndrome, immune cell-associated neurotoxicity syndrome, or graft-versus-host disease—common concerns with other cellular therapies. Only one case of Grade 2 infusion-related reaction was reported.
Cord blood units for NK cell derivation were selected from the MD Anderson Cancer Center Cord Blood Bank based on previously identified optimal criteria. Pharmacokinetic analysis showed donor NK cells peaked in patients' blood one day post-infusion, persisted up to three weeks, and successfully trafficked to tumor sites.
Future Implications
"Our trial showed the favorable safety profile and encouraging activity of AFM13-NK cells in patients with heavily pretreated refractory CD30-positive Hodgkin lymphoma," noted Dr. Nieto. "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."
The results suggest this approach could potentially transform treatment paradigms for CD30-positive lymphomas and may eventually be adapted for other malignancies, offering new hope for patients with limited therapeutic options.
