Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA.
Blood. 2021 Apr 29;137(17):2321-2325. doi: 10.1182/blood.2020009432.
The prognosis of patients with large B-cell lymphoma (LBCL) that progresses after treatment with chimeric antigen receptor (CAR) T-cell therapy targeting CD19 (CAR19) is poor. We report on the first 3 consecutive patients with autologous CAR19-refractory LBCL who were treated with a single infusion of autologous 1 × 106 CAR+ T cells per kilogram targeting CD22 (CAR22) as part of a phase 1 dose-escalation study. CAR22 therapy was relatively well tolerated, without any observed nonhematologic adverse events higher than grade 2. After infusion, all 3 patients achieved complete remission, with all responses continuing at the time of last follow-up (mean, 7.8 months; range, 6-9.3). Circulating CAR22 cells demonstrated robust expansion (peak range, 85.4-350 cells per microliter), and persisted beyond 3 months in all patients with continued radiographic responses and corresponding decreases in circulating tumor DNA beyond 6 months after infusion. Further accrual at a higher dose level in this phase 1 dose-escalation study is ongoing and will explore the role of this therapy in patients in whom prior CAR T-cell therapies have failed. This trial is registered on clinicaltrials.gov as #NCT04088890.
接受嵌合抗原受体（CAR）T 细胞疗法靶向 CD19（CAR19）治疗后进展的大 B 细胞淋巴瘤（LBCL）患者的预后较差。我们报告了前 3 例连续的自体 CAR19 难治性 LBCL 患者，他们接受了单次输注自体 1×106/kg 靶向 CD22（CAR22）的 CAR+T 细胞作为 1 期剂量递增研究的一部分。CAR22 治疗耐受性相对较好，未观察到任何高于 2 级的非血液学不良事件。输注后，所有 3 例患者均达到完全缓解，所有反应在最后一次随访时仍持续（平均 7.8 个月；范围，6-9.3）。循环 CAR22 细胞表现出强烈的扩增（峰值范围为 85.4-350 个/微升），并且在所有患者中均持续存在超过 3 个月，这些患者的影像学反应持续存在，并且在输注后 6 个月以上时循环肿瘤 DNA 相应下降。在该 1 期剂量递增研究中，更高剂量水平的进一步入组正在进行中，将探索该疗法在先前 CAR T 细胞治疗失败的患者中的作用。该试验在 clinicaltrials.gov 上注册为 #NCT04088890。
