CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Quantitative evaluation of therapy options for relapsed/refractory diffuse large B-cell lymphoma: A model-based meta-analysis.
Quantitative evaluation of therapy options for relapsed/refractory diffuse large B-cell lymphoma: A model-based meta-analysis.
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近年来,复发/难治性弥漫大B细胞淋巴瘤(r/rDLBCL)的新疗法不断涌现,但尚无对这些疗法疗效的全面定量比较。本研究通过基于模型的meta分析,比较了11种治疗策略和63种治疗方案的疗效特征。
我们发现,与单药治疗相比,联合治疗在总生存期(OS)、无进展生存期(PFS)和客观缓解率(ORR)方面具有显著获益。然而,尽管涉及化疗的治疗方案有助于显著改善ORR和PFS,但OS并未改善。在治疗策略方面,我们确定化疗联合免疫治疗序贯自体干细胞移植(ASCT)、两种不同类型免疫治疗的联合、化疗序贯ASCT、化疗联合免疫治疗,以及化疗联合两种类型免疫治疗显示出更好的疗效。在具体治疗方案方面,我们发现以下方案具有更好的疗效:利妥昔单抗联合奥英妥珠单抗;利妥昔单抗联合卡莫司汀、依托泊苷、阿糖胞苷和美法仑序贯ASCT(R-BEAM+ASCT);来那度胺联合利妥昔单抗、依托泊苷、顺铂、阿糖胞苷和甲泼尼龙;碘-131托西莫单抗联合BEAM序贯ASCT;以及化疗序贯CAR-T 细胞免疫治疗,中位OS分别为48.2、34.2、27.8、25.8和25个月。
此外,在联合治疗方面,6个月PFS与2年OS之间存在强相关性。本研究结果为r/rDLBCL治疗的临床实践和临床试验设计提供了必要的定量信息。
New therapies for relapsed/refractory diffuse large B-cell lymphoma (r/rDLBCL) have emerged in recent years, but there have been no comprehensive quantitative comparisons of the efficacy of these therapies. In this study, the efficacy characteristics of 11 types of treatment strategy and 63 treatment regimens were compared by model based meta-analysis.
We found that compared with monotherapy, association therapy had significant benefits in terms of overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).
However, whereas treatment regimens involving chemotherapy contributed to significant improvements in ORR and PFS, OS was not improved. In terms of treatment strategy, we identified chemotherapy in association with immunotherapy sequential autologous stem cell transplantation (ASCT), the association of two different types of immunotherapies, chemotherapy sequential ASCT, chemotherapy in association with immunotherapy, and chemotherapy in association with two types of immunotherapies as showing better efficacy.
With respect to specific treatment regimens, we found that the following had better efficacy: rituximab in association with inotuzumab ozogamicin; rituximab in association with carmustine, etoposide, cytarabine, and melphalan sequential ASCT (R-BEAM+ASCT); lenalidomide in association with rituximab, etoposide, cisplatin, cytarabine, and methylprednisolone; iodine-131 tositumomab in association with BEAM sequential ASCT; and chemotherapy sequential chimeric antigen receptor T-cell immunotherapy, with median OS of 48.
2, 34. 2, 27. 8, 25. 8, and 25 months, respectively.
Moreover, with respect to association therapy, there was a strong correlation between the 6-month PFS and 2-year OS. The findings of this study provide the necessary quantitative information for clinical practice and clinical trial design for the treatment of r/rDLBCL.
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