Neuroblastoma Patient Still in Remission 18 Years After CAR-T Infusion

A woman diagnosed with neuroblastoma in childhood has remained in remission for more than 18 years after being treated with an engineered CAR T-cell therapy at 4 years of age, according to follow-up of a phase I trial.

Among 19 neuroblastoma patients treated with CAR T-cell therapy, eight survived more than 5 years after infusion, including five with follow-up of more than 13 years, reported Helen Heslop, MD, of the Baylor College of Medicine in Houston, and colleagues.

“Despite using first-generation vectors that are no longer employed because of the lack of co-stimulatory domains, patients with relapsed/refractory neuroblastoma achieved long-term disease control after receiving GD2 CAR-T cell therapy, including the one patient now in remission of relapsed disease for more than 18 years,” they wrote in Nature Medicine. “This study described, to our knowledge, the longest reported survival after CAR-T therapy for active malignancy.”

Participants in the study, which enrolled from 2004 to 2009, were infused with two immune effector cell products — activated T cells expanded with OKT3 antibody and Epstein-Barr virus (EBV)-specific T cells generated by stimulation with autologous EBV-transformed lymphoblastoid cell lines. These were each transduced with first-generation CARs recognizing GD2 expressed on neuroblastoma.

As for the woman in remission for longer than 18 years, dubbed “patient 1,144,” Heslop and colleagues pointed out that she had bone lesions before receiving the CAR T-cell therapy infusion 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 therapy,” the researchers observed. “Encouragingly, she has subsequently had two full-term pregnancies with normal infants. The overall toxicities observed during this long-term follow-up were attributable to previous chemotherapy, with sensorineural hearing loss as the most common adverse event.”

Eleven of the 19 patients in the phase I trial had active relapsed diseases at the time of infusion, while the remaining eight had no evidence of active disease. Of those eight, five had a history of relapsed disease, and three were infused after completing therapy for high-risk disease. At enrollment, participants were between the ages of 3 and 20 years, and just over half were male.

Of the 11 patients with active disease at the time of infusion, three had complete responses and one had a partial response. One of the patients with a complete response subsequently relapsed, but two had sustained responses: patient 1,144 and another with a response lasting 8 years before being lost to follow-up.

Of the eight patients with no evidence of active disease at the time of infusion, five were disease free at their last follow-up between 10 and 15 years post-infusion. However, Heslop and colleagues acknowledged that since these patients had no evidence of active disease prior to their CAR T-cell therapy, “they may have already been cured.”

Event-free survival at 15 years was 31.6% for the entire cohort, including 18.2% for patients with active disease and 50% for patients with no evidence of active disease at the time of infusion. Overall survival at 15 years was 36.8% — 18.2% and 62.5% for patients with active or no active disease, respectively, prior to their CAR T-cell therapy infusion.

Twelve patients died between 2 months and 7 years after infusion due to relapsed neuroblastoma. Seven patients are alive at the last follow-up.

The authors noted that one patient developed invasive ductal carcinoma of the breast at age 32, more than a decade after infusion. They attributed this secondary malignancy to extensive chemotherapy and thoracic spinal radiation therapy before infusion, “both of which are well-documented risk factors.”

Please enable JavaScript to view the

comments powered by Disqus.