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 previous lines of immunomodulatory therapy (range: 2–9). The median follow-up was six months (range: 6–9). Results: Grade 3 to 4 neutropenia occurred in two patients and was managed with supportive care. Three patients had hypogammaglobulinemia requiring intravenous immunoglobulin replacement. 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, the Systemic Lupus Erythematosus Disease Activity Index 2000 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 European Scleroderma Trials and Research 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. (Figure presented.).