B-cell Maturation Antigen Targeted Chimeric Antigen Receptor T-cell Therapy for Refractory Systemic Lupus Erythematosus and Systemic Sclerosis.

Abstract

To evaluate the safety and preliminary efficacy of HBI0101, B-cell maturation antigen-targeted chimeric antigen receptor T-cell therapy, in patients with severe refractory systemic lupus erythematosus or systemic sclerosis. We conducted an ongoing phase 1 trial of HBI0101 in six patients with severe systemic lupus erythematosus (n=3) or systemic sclerosis (n=3). The median age was 41 years (range, 21-65), the median disease duration was 2.7 years (range, 1.1-20.5), and patients had received a median of 3.5 prior lines of immunomodulatory therapy (range, 1- 9). The median follow-up was 6 months (range, 6-9). Grade 3-4 neutropenia occurred in two patients and was managed with supportive care. Cytokine-release syndrome occurred in five patients (grade 2 in three and grade 1 in two) and was absent in one patient. No immune effector cell associated neurotoxicity syndrome was observed. In systemic lupus erythematosus, SLEDAI-2K decreased to 0 in two patients and to 4 in one patient. In systemic sclerosis, skin involvement improved in all three patients with reductions in modified Rodnan skin score and EUSTAR activity indices. HBI0101 demonstrated an acceptable safety profile and early clinical activity in patients with severe refractory systemic lupus erythematosus or systemic sclerosis, supporting further prospective evaluation.