A new type of remodeled CAR T-cell treatment is just as effective as the original therapy but may result in fewer neurologic side effects, researchers reported in Nature Medicine.
The remodeled cells replace the hinge and transmembrane domains from the original CAR and also change a murine protein for a more similar human protein. The new CAR T cells still target CD19, but the researchers found that they produce lower levels of cytokines, which may account for the reduction in neurotoxicity.
The researchers studied the new cells in 20 patients with B-cell lymphoma and compared the results to an earlier study of the original CAR T cells in 22 patients with B-cell lymphoma. In the new study, four patients (20%) developed neurotoxicity, but it was mild in all but one patient who was successfully managed with steroid treatment. In the older study, 17 patients (77%) had neurologic toxicities, which was severe in 11 patients (50%). Two patients (10%) in the new trial and four patients (18%) in the older study had severe cytokine release syndrome. In both trials, 55% of the patients went into complete remission.
“It’s heartening to see very good efficacy for this CAR T-cell product in addition to the low toxicity,” the researchers said.