State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Tianjin Institutes of Health Science, Tianjin, China.
J Immunother Cancer. 2024 Apr 16;12(4):e008857. doi: 10.1136/jitc-2024-008857.
Approximately two-thirds of patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) do not respond to or relapse after anti-CD19 chimeric antigen receptor T (CAR T)-cell therapy, leading to poor outcomes. Previous studies have suggested that intensified lymphodepletion and hematological stem cell infusion can promote adoptively transferred T-cell expansion, enhancing antitumor effects. Therefore, we conducted a phase I/II clinical trial in which CNCT19 (an anti-CD19 CAR T-cell) was administered after myeloablative high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) in patients with R/R LBCL.
Transplant-eligible patients with LBCL who were refractory to first-line immunochemotherapy or experiencing R/R status after salvage chemotherapy were enrolled. The study aimed to evaluate the safety and efficacy of this combinational therapy. Additionally, frozen peripheral blood mononuclear cell samples from this trial and CNCT19 monotherapy studies for R/R LBCL were used to evaluate the impact of the combination therapy on the in vivo behavior of CNCT19 cells.
A total of 25 patients with R/R LBCL were enrolled in this study. The overall response and complete response rates were 92.0% and 72.0%, respectively. The 2-year progression-free survival rate was 62.3%, and the overall survival was 68.5% after a median follow-up of 27.0 months. No unexpected toxicities were observed. All cases of cytokine release syndrome were of low grade. Two cases (8%) experienced grade 3 or higher CAR T-cell-related encephalopathy syndrome. The comparison of CNCT19 in vivo behavior showed that patients in the combinational therapy group exhibited enhanced in vivo expansion of CNCT19 cells and reduced long-term exhaustion formation, as opposed to those receiving CNCT19 monotherapy.
The combinational therapy of HDT/ASCT and CNCT19 demonstrates impressive efficacy, improved CNCT19 behavior, and a favorable safety profile.
ChiCTR1900025419 and NCT04690192.
大约三分之二的复发或难治性大 B 细胞淋巴瘤（R/R LBCL）患者对抗 CD19 嵌合抗原受体 T（CAR T）细胞治疗无反应或治疗后复发，导致预后不良。先前的研究表明，强化淋巴细胞耗竭和造血干细胞输注可以促进过继转移 T 细胞的扩增，增强抗肿瘤作用。因此，我们进行了一项 I/II 期临床试验，在复发/难治性大 B 细胞淋巴瘤患者中，在清髓性大剂量化疗和自体干细胞移植（HDT/ASCT）后给予 CNCT19（一种抗 CD19 CAR T 细胞）。
入组的 LBCL 患者对一线免疫化疗耐药或挽救化疗后出现 R/R 状态，适合移植。本研究旨在评估这种联合治疗的安全性和有效性。此外，还使用该试验和 CNCT19 治疗 R/R LBCL 的单药治疗研究的冷冻外周血单个核细胞样本，评估联合治疗对 CNCT19 细胞体内行为的影响。
共纳入 25 例 R/R LBCL 患者。总缓解率和完全缓解率分别为 92.0%和 72.0%。中位随访 27.0 个月后，2 年无进展生存率为 62.3%，总生存率为 68.5%。未观察到意外毒性。所有细胞因子释放综合征均为低级别。2 例（8%）发生 3 级或以上 CAR T 细胞相关脑病综合征。CNCT19 体内行为比较显示，联合治疗组患者体内 CNCT19 细胞的扩增增强，长期耗竭形成减少，而接受 CNCT19 单药治疗的患者则相反。
HDT/ASCT 和 CNCT19 的联合治疗具有显著疗效，改善了 CNCT19 的行为，且具有良好的安全性。
ChiCTR1900025419 和 NCT04690192。
Zotero 插件
