Clinical trials with the CAR-T therapy, tisagenlecleucel, show continued high rates of complete remission in children and young adults with short-lived and reversible side effects. These updated findings are published in a recent issue of the New England Journal of Medicine.
In chimeric antigen receptor T-cell (CAR-T) immunotherapy, a patient’s own T cells are isolated and engineered to express receptors highly specific to tumor cells. The approach used in the study was developed by a team led by Carl June, MD, at the University of Philadelphia and licensed to Novartis as tisagenlecleucel. In August 2017, in collaboration with the Children's Hospital of Philadelphia, this became the first FDA-approved gene-therapy based treatment in the US.
The phase 2 global study, spanning 25 centers, focused on a single cohort of 75 children to young adults up to age 25 with CD19+ relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). The participants received an infusion of tisagenlecleucel and evaluated for efficacy. The primary aim was to determine the 3-month overall remission rate, defined as complete remission with or without complete recovery of blood counts.
Following treatment, 61 patients (81%) showed remission after at least three months. Of those, 80% were relapse-free after six months, and 59% at twelve months. Overall survival in all 75 patients was 90% at six months and 76% at 12 months. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. Authors concluded that the treatment “provided durable remission with long-term persistence.”
"This expanded, global study of CAR T-cell therapy gives us further evidence of how remarkable this treatment can be for our young patients in whom all other treatments failed," said lead author Shannon L. Maude. "Our data show not only can we can achieve longer-term durable remissions, and longer-term survival for our patients, but that these personalized, cancer-fighting cells can remain in the body for months or even years, effectively doing their job."
As with earlier studies of CAR T-cell treatment, the most common side effect was a severe flu-like condition called cytokine release syndrome (CRS), involving high fever, muscle pain, neurologic symptoms, and circulatory and respiratory problems. This occurred in 77% of the patients, but had treatable and transient effects, manageable with supportive care.
"One of our more challenging questions - 'can we manage the serious side effects of CAR T-cell therapy?' - was asked, and answered in this global study," said senior co-author Stephan Grupp. "Some of our patients get very sick, but we showed that most toxic effects can be short-lived and reversible, with the potential for our patients to achieve durable, complete remissions. That's a pretty amazing turnaround for the high-risk child who, up until now, had little chance of surviving."
The research team is pursuing ongoing clinical trials, studying ways to mitigate serious side effects and overcome relapse.