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复发/难治性弥漫性大B细胞淋巴瘤治疗方案的定量评估:基于模型的荟萃分析。

Quantitative evaluation of therapy options for relapsed/refractory diffuse large B-cell lymphoma: A model-based meta-analysis.

作者信息

Li Ting, Yu Jiesen, Hou Mengyuan, Zha Sijie, Cheng Qingqing, Zheng Qingshan, Li Lujin

机构信息

Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, No.1200 Cailun Road, Shanghai 201203, China.

Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, No.1200 Cailun Road, Shanghai 201203, China.

出版信息

Pharmacol Res. 2023 Jan;187:106592. doi: 10.1016/j.phrs.2022.106592. Epub 2022 Dec 5.

Abstract

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.

摘要

近年来出现了复发性/难治性弥漫性大B细胞淋巴瘤(r/rDLBCL)的新疗法,但尚未对这些疗法的疗效进行全面的定量比较。在本研究中,通过基于模型的荟萃分析比较了11种治疗策略和63种治疗方案的疗效特征。我们发现,与单一疗法相比,联合疗法在总生存期(OS)、无进展生存期(PFS)和客观缓解率(ORR)方面具有显著优势。然而,虽然涉及化疗的治疗方案使ORR和PFS有显著改善,但OS并未改善。在治疗策略方面,我们确定化疗联合免疫疗法序贯自体干细胞移植(ASCT)、两种不同类型免疫疗法的联合、化疗序贯ASCT、化疗联合免疫疗法以及化疗联合两种免疫疗法显示出更好的疗效。关于具体治疗方案,我们发现以下方案疗效更好: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;以及化疗序贯嵌合抗原受体T细胞免疫疗法,中位OS分别为48.2、34.2、27.8、25.8和25个月。此外,关于联合疗法,6个月PFS与2年OS之间存在很强的相关性。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。

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