In this trial, the largest study to date of a CAR T-cell therapy for such patients, the researchers co-administered two CAR T-cell therapies, one targeting CD19 and the other targeting CD22.
The results showed that 192 of 194 patients (99%) achieved a complete remission.
The combined overall 12-month event-free survival was 73.5%.
The study was published online in the Journal of Clinical Oncology.
These results are better than what has been reported for CAR T cells that are already on the market. These products, which target CD19, have achieved complete remission in 85.5% of cases and a 12-month event-free survival of 52.4% in children with B-ALL.
“We do believe [this approach] will become standard of care,” said study author Ching-Hon Pui, MD, of the departments of oncology, pathology, and global pediatric medicine, St. Jude Children’s Research Hospital, Memphis.
He noted that this work builds on the huge success that has already been achieved in this field with CAR T-cell products directed at CD19. The first of these products to reach the market was tisagenlecleucel-T (Novartis).
“To put this study in context, the first child who received CAR T-cell therapy for B-ALL after multiple relapses has recently celebrated her 10-year cancer-free survival milestone, and we hope that our finding will result in many more such milestones,” he said.
These new results are very impressive, said Stephen P. Hunger, MD, an expert commenting for the American Society of Clinical Oncology, which highlighted the research in a press release. “They were also able to treat almost 200 patients in a relatively short time.”
Hunger pointed out that dual administration and targeting is not a new idea and is one of the strategies that is currently under investigation. But it is too early to consider this to be the standard of care, he said. “We want to see it replicated in other centers and to see longer follow-up,” said Dr. Hunger, who is Distinguished Chair in Pediatrics and director of the center for childhood cancer research at Children’s Hospital of Philadelphia. “We can establish this as a first step down the road, and we will see if others will achieve similar results.”
Strategy of dual targeting
Despite the success CAR T-cell therapy in childhood leukemia, the currently available products have limitations, Dr. Pui and colleagues note.
About half of patients treated with CD19 CAR T cells experience relapse within 1 year, owing either to loss of CAR T-cell persistence or to loss of CD19 antigen because of splice variants, acquired genetic mutations, or lineage switch.
With further treatment with CAR T cells directed against CD22, 70%-80% of patients who failed CD19 CAR T will achieve into complete remission. However, most will experience relapse.
Recent efforts in the field have turned to exploring the safety and feasibility of CAR T cells that target both CD19 and CD22. The results were not superior to those of the CD19 CAR T-cell therapy given alone, although sequential treatment has yielded promising response rates, the authors note.
They hypothesized that co-administration of CD19- and CD22-targeted CAR T cells would improve efficacy, as it could forestall the development of drug resistance.