CELL INTELLIGENCE · 肿瘤细胞治疗研究

IMPORTANCE: Patients with high-risk newly diagnosed multiple myeloma (NDMM) often have poor outcomes with standard treatments, necessitating novel effective frontline therapies to enhance clinical outcomes. GC012F, a B-cell maturation antigen/CD19 dual-targeting chimeric antigen receptor (CAR) T-cell therapy, has been developed on the novel FasTCAR platform. Notably, its use as a frontline therapy for patients with high-risk NDMM who are eligible for transplant has not been thoroughly explored. OBJECTIVE: To examine the safety, pharmacokinetics, and patient health and survival outcomes associated with GC012F in individuals with NDMM. DESIGN, SETTING, AND PARTICIPANTS: Patients were enrolled in this single-arm, open-label phase 1 cohort study between June 28, 2021, and June 1, 2023 (the data cutoff date). All patients included in this study were treated at a single center, Shanghai Changzheng Hospital. The patients in the efficacy evaluation were followed up for a minimum period of 3 months. INTERVENTION: Patients underwent 2 cycles of induction therapy, followed by GC012F infusion (at 1 105 cells/kg, 2 105 cells/kg, or 3 105 cells/kg). MAIN OUTCOMES AND MEASURES: The primary goals were to assess the safety, efficacy, and pharmacokinetics of GC012F at various dose levels. RESULTS: Of 22 patients receiving GC012F treatment, 6 experienced mild to moderate cytokine release syndrome (grade 1-2) and none experienced neurotoxic effects. Nineteen patients were included in the efficacy evaluation, and all 19 patients showed stringent complete responses and achieved minimal residual disease negativity. The treatment's effectiveness was consistent across different dose levels. GC012F demonstrated a rapid response, with a median time to first stringent complete response of 84 days (range, 26-267 days) and achieving minimal residual disease negativity within 28 days (range, 23-135 days). The CAR T-cell expansion was robust, with a median peak copy number of 60 652 copies/ g genomic DNA (range, 8754-331 159 copies/ g genomic DNA), and the median time to median peak copy number was 10 days (range, 9-14 days). CONCLUSIONS AND RELEVANCE: The findings of this single-arm, open-label phase 1 cohort study suggest that GC012F may be a safe treatment associated with positive health and survival outcomes for patients with high-risk NDMM eligible for transplant. Owing to the small sample size, further studies with larger cohorts and longer follow-up durations are needed.