CAR-T Therapy Shows Persistent Benefits in Young Leukemia Patients

Three-quarters of Kymriah patients survive after a year

Updated results from a global clinical trial of the CAR T-cell therapy tisagenlecleucel (Kymriah, Novartis) show that children and young adults continued to show high rates of durable, complete remission of their high-risk form of acute lymphoblastic leukemia (ALL), according to a study published in the New England Journal of Medicine. Most side effects were short-lived and reversible

Based on previous findings, the FDA approved tisagenlecleucel in August 2017 for children and young adults up to 25 years of age with B-cell ALL that is refractory or in second or later relapse. It was the first FDA-approved gene therapy, as well as the first FDA-approved CAR T-cell therapy.

The updated results report new data from the Novartis-sponsored ELIANA trial, conducted in 25 centers in 11 countries worldwide.

Chimeric antigen receptor T-cell therapy (CAR-T) genetically modifies a patient's immune cells to make them seek out and kill leukemia cells. The approach was developed by a team led by Carl June, MD, of the Perelman School of Medicine at the University of Pennsylvania. That team collaborated with Children's Hospital of Philadelphia (CHOP), the first institution to use the therapy in children with leukemia.

The current study includes longer-term follow-up of safety and efficacy data in 75 patients aged 25 and younger.

"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, MD, PhD, a pediatric oncologist at CHOP and Assistant Professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania.

In the 75 children and young adults who received the CAR T cells, 61 (81%) had a response to treatment, defined as complete remission with or without complete recovery of blood counts, after at least three months of follow-up. Relapse-free survival in those 61 patients was 80% at six months after treatment, and 59% at 12 months. Overall survival in all 75 patients was 90% at six months and 76% at 12 months. The survival rates, say the authors, are evidence that the early response rates were durable. In the absence of CAR T-cell therapy, patients with multiple relapsed or refractory B-cell ALL face a poor prognosis.

Accompanying the durable responses, the CAR T cells persisted in the patients for as long as 20 months, with a median persistence of 168 days at the point at which data were analyzed for this study. All patients in the trial received a single infusion of the CAR T cells.

In line with earlier studies of CAR T-cell treatment, the most common treatment-related 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. Nearly half of the 75 patients received intensive care unit treatment to manage CRS, but the effects were treatable and transient.

"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 Stephan A. Grupp, MD, PhD, the Section Chief of Cell Therapy and Transplant at CHOP and a Professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania. Grupp was lead investigator of this phase 2 trial. "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.

Source: Children’s Hospital of Philadelphia; January 31, 2018.