The survival rates increased by 20% for children who have high-risk neuroblastoma who participated in a St. Jude Children’s Research Hospital clinical trial, which included the first monoclonal antibody to be produced onsite. The Journal of Clinical Oncology published the results today.
Neuroblastoma is a cancer of mature nerve cells of the sympathetic nervous system. The tumor is diagnosed in approximately 700 people each year in the U.S., mostly children 5 years old or younger. Despite aggressive therapy, nearly half of patients with high-risk neuroblastoma die from their disease.
The results of the St. Jude phase II clinical trial revealed significantly higher survival rates for newly diagnosed patients who received treatment with the humanized monoclonal antibody hu14.18K322A along with standard therapy for high-risk illnesses. Three-year disease-free survival was 73.7% for the 64 children who participated in the study. The overall survival rate was 86%.
I have been treating high-risk neuroblastoma patients for more than 30 years, and have never seen such remarkable results in them. This is the most important outcome ever reported for patients with high-risk neuroblastoma.
Wayne Furman, M.D. First author and co-author, Department of Oncology, St. Jude Children’s Research Hospital
Furman said that if the results of this study are confirmed in an additional multi-center clinical trial then the chemoimmunotherapy outlined in this study could be a standard treatment for patients with high risk of developing diseases.
Monoclonal anti-GD2 antibody, with an additional difference
Hu14.18322A was created in the laboratory to connect GD2 antibodies on the surface of neuroblastoma tumor cells. The binding activates immune cells to attack tumor cells and eliminate them. The monoclonal antibody in this study was created at the Children’s GMP, LLC., on the St. Jude campus, by using a method that was refined by the scientists at the manufacturing facility.
Hu14.18322A was not the first monoclonal antineurodepressant to be developed for neuroblastoma treatment. GD2 antibodies are found on a variety of normal tissues, including cells in the peripheral nervous system. Contrary to other monoclonal anti-GD2 antibodies, hu14.18322A has been engineered to limit the side effects that are dose-limiting and pain.
Phase II comprised hu14.18K322A treatment. The therapy included high-dose chemotherapy, immunotherapy with granulocyte-macrophage colony-stimulating factor and interleukin 2, surgery, autologous blood stem cell transplantation and radiation. Patients also received opioids to treat pain. These and other studies have shown that mixing hu14.18K322A and high-dose chemotherapy can have a synergistic impact.
Dose is the key?
Dinutuximab was the first anti-GD2 monoclonal antibody approved by the U.S. Food and Drug Administration to treat neuroblastoma with high risk of recurrence.
Patients in the St. Jude phase 2 clinical trial experienced significantly higher doses hu14.18K322A than the maximum approved dose.
Furman stated that dinutuximab can’t be given at the same dose. One of the unanswered questions is whether patients received a higher dose or if hu14.18K322A was a better antibody.
EMD Serono owns Hu14.18K322A, a division German-based Merck KGaA. The monoclonal antibody was developed for clinical use at St. Jude. The hu14.18K322A used in this study was produced in the Children’s GMP, LLC, an institution on the St. Jude campus that produces biopharmaceuticals such as monoclonal antibodies in accordance with federal guidelines.
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