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

OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.