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从突破到蓝图:复发和难治性大 B 细胞淋巴瘤中不断演变的证据与未来方向

英文原题:From breakthroughs to blueprints: evolving evidence and future directions in relapsed and refractory large B-cell lymphoma.

PubMed 2026/06/11(内容时间) Blood Q1 · IF 23.9(JCR 2025)

研究概要

复发或难治性大B细胞淋巴瘤(R/R LBCL)的治疗格局已发生快速而深刻的变化,这主要由细胞疗法、双特异性抗体和下一代抗体药物偶联物(ADCs)推动。

中文摘要

复发或难治性大B细胞淋巴瘤(R/R LBCL)的治疗格局已发生迅速而深刻的变化,其驱动力来自细胞疗法、双特异性抗体和下一代抗体药物偶联物(ADC)。这些进展重新定义了历史标准,同时暴露出在试验设计、生物学认识和治疗序贯方面持续存在的差距。近期随机研究表明,以ADC和双特异性抗体为锚定的方案可以优于传统化疗对照,但其解读受到地域异质性、选择性入组以及缺乏当代对照臂的试验激增的阻碍。下一代方法,包括双特异性抗体-ADC联合方案、双靶点CAR-T 细胞疗法(CAR-T)构建体,以及明确设计用于规避抗原逃逸的策略,正准备挑战长期存在的治疗层级,并可能将治愈潜力扩展至不适合接受CAR-T或CAR-T后复发的患者。该领域目前正处于一个拐点,治疗创新的推进速度快于指导实践所需的证据基础设施。要实现持久、公平的获益,需要与当前CAR-T标准一致的对照臂、协调统一的入组标准、前瞻性分子谱分析,以及能够随标准治疗演进的适应性试验平台。随着ADC和双特异性抗体向更早期治疗推进并扩散至社区实践,核心挑战不再仅仅是开发有效疗法,而是创建生物学上合理、可及且可解读的路径,使可耐受的治愈性治疗成为所有R/R LBCL患者现实且普遍的目标。

展开英文摘要原文

The therapeutic landscape for relapsed or refractory large B-cell lymphoma (R/R LBCL) has undergone rapid and profound change, driven by cellular therapies, bispecific antibodies, and next-generation antibody-drug conjugates (ADCs). These advances have redefined historical standards while exposing persistent gaps in trial design, biological insight, and therapeutic sequencing. Recent randomized studies show that ADC- and bispecific-anchored regimens can outperform legacy chemotherapy comparators, yet interpretation is hindered by geographic heterogeneity, selective enrollment, and a proliferation of trials lacking contemporary control arms. Next-generation approaches, including bispecific-ADC combinations, dual-target chimeric antigen receptor T-cell therapy (CAR-T) constructs, and strategies explicitly designed to circumvent antigen escape, are poised to challenge long-standing therapeutic hierarchies and may broaden curative potential to patients who are ineligible for, or relapse after, CAR-T. The field now stands at an inflection point at which therapeutic innovation is advancing faster than the evidence infrastructure required to guide practice. Delivering durable, equitable benefit will require control arms aligned with current CAR-T standards, harmonized eligibility criteria, prospective molecular profiling, and adaptive trial platforms capable of evolving with the standard of care. As ADCs and bispecifics move earlier in treatment and diffuse into community practice, the central challenge is no longer the development of active therapies alone, but the creation of biologically rational, accessible, and interpretable pathways that make tolerable, curative treatments a realistic and universal goal for all patients with R/R LBCL.

论文信息

作者
Kamdar M、Bartlett NL
第一作者单位
Division of Hematology, Department of Medicine, University of Colorado Cancer Center, Aurora, CO.
通讯作者单位
Division of Oncology, Department of Medicine, Siteman Cancer Center, St Louis, MO.United States
文献类型
综述
期刊
Blood2026 Jun 11
原文标识
PubMed 41871044 · DOI 10.1182/blood.2025030859