A phase I clinical trial of first-generation chimeric antigen receptor T-cell therapy in pediatric patients with neuroblastoma demonstrated sustained treatment responses, according to long-term follow-up data.

Researchers, who conducted the trial at Baylor College of Medicine from 2004 to 2009, treated 19 children with two types of T cells expressing GD2-targeting chimeric antigen receptors (CARs) without costimulatory domains. Of 11 patients with active disease at infusion, 3 achieved complete response, with 2 maintaining long-term remission—1 for 8 years until lost to follow-up, and the other for more than 18 years.

"Patient 1,144—who is alive at more than 18 years after infusion—had bone lesions before receiving [CAR T-cell therapy] and attained a complete remission. She has never required any other therapy and is likely the longest-surviving patient with cancer who received [CAR T-cell] therapy," the researchers reported in Nature Medicine.

Among eight patients with no evidence of disease at treatment, five remained disease-free at final follow-up between 10 and 15 years postinfusion. The 15-year event-free survival was 31.6% overall (18.2% for patients with active disease and 50% for those with no evidence of disease, P = .044).

The trial utilized both activated T cells (ATCs) and Epstein-Barr virus–specific T cells (VSTs), each engineered with distinct barcode sequences allowing tracking of cell persistence. Long-term survivors showed significantly longer detection of transgenes compared to nonsurvivors (P = .0002).

"Despite using first-generation vectors that are no longer employed because of the lack of costimulatory domains, patients with relapsed/refractory neuroblastoma achieved long-term disease control after receiving GD2 CAR-T cell therapy," the authors wrote.

Notably, one patient developed breast cancer 12 years post-treatment at age 32, which was attributed to receipt of prior chemotherapy and radiation exposure rather than CAR T-cell therapy. The most common treatment-related adverse event was sensorineural hearing loss.

The researchers concluded, "This study describes, to our knowledge, the longest reported survival after [CAR T-cell] therapy for active malignancy, demonstrating that GD2 CAR-ATC/VST therapy can safely produce up to more than 18 years of complete remission in children with refractory/relapsed neuroblastoma, without evidence of malignancy or other long-term sequalae attributed to [CAR T-cell] therapy."

Full disclosures can be found in the study.