Promising Initial Data for Investigational Anti-CD19 CAR T-Cell Therapy in Autoimmune Diseases

Two ongoing phase I, multicenter, open-label studies are evaluating an investigational, CD19-targeting chimeric antigen receptor (CAR) T-cell therapy for severe refractory autoimmune diseases. Interim data from these studies were presented at the 66th American Society of Hematology Annual Meeting & Exposition in San Diego, California.

The therapy, BMS-986353 (CC-97540), is distinguished by the new NEX-T manufacturing process, featuring faster production time and improved phenotypic attributes of the resulting CAR T-cell product.

“BMS-986353 demonstrates a low rate of low grade [cytokine release syndrome (CRS)] and [immune effector cell associated neurotoxicity syndrome (ICANS)] events. Preliminary data suggest promising efficacy in patients with [systemic lupus erythematosus (SLE)] despite discontinuation of all lupus therapies,” wrote lead author Fabian Mueller, MD, of University Hospital Erlangen, Erlangen, Germany.

The two studies had a total cohort of seven patients—five with SLE, one with systemic sclerosis (SSc), and one with relapsing-remitting multiple sclerosis (MS). The patients’ autoimmune-directed therapies were tapered, and two to nine days after lymphodepletion, they received BMS-986353 infusion. Patients received the therapy in doses of 10 × 10⁶ or 25 × 10⁶ CAR T cells, except for the patient with MS who received a dose of 5 × 10⁶ CAR T cells. The total cohort had a median treatment follow-up of 167.5 days.

All seven patients were evaluable for safety, and no dose-limiting toxicities were reported. There were two occurrences of CRS, grade 1 in a patient with SLE and grade 2 in the patient with SSc; both resolved within one day. Grade 1 ICANS developed in the patient with SSc but resolved in one day. Four patients with SLE and the patient with MS experienced grade 3 or 4 transient lymphodepletion-related cytopenias, but there were no prolonged grade 3 or worse severity cytopenias.

In the group of four patients who were evaluable for efficacy, there was a notable median SLE Disease Activity Index 2000 score improvement of 4.0 points and a median Physician’s Global Assessment score improvement of 0.55 points.

“All patients remain off autoimmune-directed therapies without evidence of disease flare,” noted Dr. Mueller.

The investigators highlighted that in patients with SLE who received the 10 × 10⁶ CAR T-cell dose of BMS-986353, an amount only one-tenth the recommended phase II dose of lisocabtagene maraleucel (liso-cel), complete B-cell depletion was achieved as well as CAR T-cell expansion comparable to results with liso-cel.

Reference

Mueller F, Patel K, Reshef R, et al. Tolerability, efficacy, pharmacokinetics, and pharmacodynamics of BMS-986353 (CC-97540), a CD19-directed chimeric antigen receptor (CAR) T cell therapy manufactured using a next-generation process, for severe, refractory autoimmune diseases: updated data from ongoing phase 1, multicenter, open-label studies. Abstract #2088. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.