Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
J Clin Oncol. 2022 Jul 10;40(20):2246-2256. doi: 10.1200/JCO.21.01676. Epub 2022 Mar 25.
A combination of anti-B-cell maturation antigen (BCMA) and anti-CD19 chimeric antigen receptor (CAR) T cells induced high response rates in patients with relapsed or refractory (R/R) multiple myeloma (MM), but long-term outcomes have not been assessed yet.
In this single-arm, phase II trial, patients with R/R MM received a combination of anti-BCMA CAR T cells and anti-CD19 CAR T cells at a dose of 1 × 10 cells/kg, after receiving a conditioning chemotherapy consisting of cyclophosphamide and fludarabine. The overall response, long-term outcomes, and safety were assessed, as were their associations with clinical and disease characteristics.
Of 69 enrolled patients, 62 received the combined infusion of anti-BCMA and anti-CD19 CAR T cells with a median follow-up of 21.3 months. The overall response rate was 92% (57/62), and complete response or better was observed in 37 patients (60%). Minimal residual disease-negativity was confirmed in 77% (43/56) of the patients with available minimal residual disease detection. The estimated median duration of response was 20.3 months (95% CI, 9.1 to 31.5). The median progression-free survival was 18.3 months (95% CI, 9.9 to 26.7), and the median overall survival was not reached. Patients with extramedullary disease had significantly inferior survival. Fifty-nine patients (95%) had cytokine release syndrome, with 10% grade 3 or higher. Neurotoxic events occurred in seven patients (11%), including 3% grade 3 or higher. Late adverse effects were rare, except for B-cell aplasia, hypogammaglobulinemia, and infections.
The combination of anti-BCMA and anti-CD19 CAR T cells induced durable response in patients with R/R MM, with a median progression-free survival of 18.3 months and a manageable long-term safety profile.
抗 B 细胞成熟抗原 (BCMA) 和嵌合抗原受体 (CAR) 抗 CD19 T 细胞的联合应用在复发或难治性 (R/R) 多发性骨髓瘤 (MM) 患者中诱导了高反应率，但尚未评估其长期结果。
在这项单臂、二期试验中，R/R MM 患者在接受环磷酰胺和氟达拉滨组成的预处理化疗后，以 1×10 细胞/kg 的剂量接受抗 BCMA CAR T 细胞和抗 CD19 CAR T 细胞的联合输注。评估了总体反应、长期结果和安全性，并评估了它们与临床和疾病特征的关系。
在 69 名入组患者中，62 名患者接受了抗 BCMA 和抗 CD19 CAR T 细胞的联合输注，中位随访时间为 21.3 个月。总体反应率为 92%（57/62），37 名患者（60%）观察到完全缓解或更好。在可进行微小残留病灶检测的 56 名患者中，77%（43/56）证实微小残留病灶阴性。中位缓解持续时间为 20.3 个月（95%CI，9.1 至 31.5）。中位无进展生存期为 18.3 个月（95%CI，9.9 至 26.7），总生存期未达到。有髓外疾病的患者生存明显较差。59 名患者（95%）有细胞因子释放综合征，其中 10%为 3 级或更高。7 名患者（11%）发生神经毒性事件，包括 3%为 3 级或更高。除 B 细胞发育不全、低丙种球蛋白血症和感染外，晚期不良反应罕见。
抗 BCMA 和抗 CD19 CAR T 细胞的联合应用在 R/R MM 患者中诱导了持久的反应，中位无进展生存期为 18.3 个月，长期安全性可管理。
