Long-Term Follow-Up of CAR T in ALL Indicates Early Treatment Extends Survival

A long-term follow-up analyzing the toxic effects and results from a phase 1 clinical trial of adult patients with relapsed B-cell acute lymphoblastic leukemia (ALL) who were treated with CD19-specific chimeric antigen receptor (CAR) T cells found patients with low disease burden had a longer medial overall survival (OS) and a lower incidence of toxicity.

The study, published in New England Journal of Medicine, had 3 stages to evaluate safety and efficacy of 2 doses of CAR T cells and conditioning chemotherapy regimens. A total of 53 patients received 19-28z CAR T cells. The safety outcomes that the researchers focused on were incidence of cytokine release syndrome (CRS) and neurotoxic events. They also studied complete remission (CR) rate and OS and EFS.

“We hypothesized that the safety and long-term efficacy of 19-28z CAR T cells may be associated with clinical characteristics of the patients, disease characteristics, the treatment regimen, and the kinetics of T-cell expansion,” the authors wrote.

They found that CRS occurred in 26% of the patients, including 1 patient who died, and the rate of severe neurotoxicity was 42%. There was CR in 83% of patients. The median OS was 12.9 months and the median EFS was 6.1 months. The median follow-up time was 29 months.

The results, which represent the longest follow-up of people with ALL treated with CAR T therapy, “confirms the power of CAR T cells,” Jae Park, MD, a medical oncologist at Memorial Sloan Kettering (MSK) Cancer Center and the principal investigator of the phase 1 trial, said in a statement.

“With the long follow-up, we were able to demonstrate for the first time that patients with a lower disease burden benefited the most from CAR therapy, with significantly improved survival and reduced toxicity,” he said. “We are very encouraged by this progress and are eager to continue our work with these living therapies to provide new, better, and safer treatment options for patients.”

The OS was 12.9 months, but patients with a low disease burden had a median OS of 20.1 months.

While the findings of the study are suggestive and warrant confirmation in a prospective trial, Michel Sadelain, MD, PhD, director of MSK’s Center for Cell Engineering and the study’s lead author, said that the findings have major implications for the future.

“In recent years, we have witnessed many clinical studies that primarily focused on early response rates and toxicities in patients treated with CAR T cells. With the results of this study, we can begin to appreciate the long-term benefit and outcomes of this therapy,” Sadelain said.

References

Park JH, Rivière I, Gonen M, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378(5):449-459. doi: 10.1056/NEJMoa1709919.