决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Daratumumab for CD20(-)CD38(+) Relapsed/Refractory Diffuse Large B-Cell Lymphoma.
Daratumumab for CD20(-)CD38(+) Relapsed/Refractory Diffuse Large B-Cell Lymphoma.
1 年 OS 率为 75%,1 年 PFS 率为 50%,mOS 为 12 个月。
接受利妥昔单抗方案治疗的复发/难治性弥漫大B细胞淋巴瘤(R/R DLBCL)患者,CD20表达水平常会降低。更换靶蛋白、采用新的靶向化疗已成为治疗R/R DLBCL的一项热门方向。本研究旨在探讨,对于CD20阴性、CD38阳性的R/R DLBCL患者,尤其是抗CD20单克隆抗体治疗无应答者,达雷妥尤单抗能否作为靶向药物单药或联合化疗的有效替代方案,以及其是否有助于后续CAR-T 细胞免疫治疗。研究回顾性收集了4例接受多线达雷妥尤单抗联合化疗的CD20阴性、CD38阳性R/R DLBCL患者。符合条件者随后接受CAR-T治疗。研究者还成功构建了小鼠异种移植肿瘤模型。评估显示,4例接受达雷妥尤单抗联合化疗的患者治疗后均有不同程度缓解,包括完全缓解(CR)2例、部分缓解(PR)1例和疾病稳定(SD)1例。1年总生存率为75%,1年无进展生存率为50%,中位总生存期为12个月。不良反应程度中等且可逆,未发生治疗相关死亡。达雷妥尤单抗治疗使其中2例患者成功过渡至CAR-T治疗;其中出现1级细胞因子释放综合征(CRS)。这些病例显示,达雷妥尤单抗联合治疗用于CD20阴性、CD38阳性R/R DLBCL具有良好应用前景,并有助于衔接CAR-T治疗。
Patients with R/R DLBCL (relapsed/refractory diffuse large B-cell lymphoma) treated with rituximab-based regimens often have a reduction in the expression level of CD20. Replacement of target proteins for new targeted chemotherapy has become a popular direction for the treatment of R/R DLBCL. To investigate whether Daratumumab can be an effective alternative to targeted agents as monotherapy or combination chemotherapy in patients with CD20-CD38+ R/R DLBCL who have failed to respond to CD20 monoclonal antibody treatment and its adjuvant effect on subsequent CAR-T (chimeric antigen receptor T-cell immunotherapy). A total of four CD20-CD38+ R/R DLBCL patients treated with multiple lines of Daratumumab-based combination chemotherapy were retrospectively collected. For eligible patients, CAR-T therapy was used afterwards. Also, the authors successfully constructed allografted tumour models in mice. Relevant evaluation showed that four patients who received Daratumumab combination chemotherapy had varying degrees of remission after treatment, including 2 CR, 1 PR and 1 SD. The 1-year OS rate was 75%, the 1-year PFS rate was 50% and mOS was 12 months. Adverse effects were moderate and reversible, and no treatment-related deaths occurred. Daratumumab therapy led to a successful transition to CAR-T in two patients. Among them, grade 1 CRS occurred. These cases demonstrated that Daratumumab combination therapy has a good application prospect in the treatment of CD20-CD38+ R/R DLBCL and is helpful for the bridge of CAR-T therapy.
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