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

These advances have redefined historical standards while exposing persistent gaps in trial design, biological insight, and therapeutic sequencing.

这些进展重新定义了历史标准，同时暴露了试验设计、生物学洞察和治疗序列方面的持续差距。

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.

最近的随机研究显示，ADC和双特异性锚定方案可以胜过传统的化疗对照组，然而由于地理异质性、选择性入组以及缺乏当代对照组的试验激增，解释受到了阻碍。

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.

下一代方法，包括双特异性ADC组合、双靶点嵌合抗原受体T细胞疗法（CAR-T）构建体，以及旨在绕过抗原逃逸的策略，正准备挑战长期存在的治疗等级制度，并可能将治愈潜力扩大到那些不符合CAR-T治疗或在CAR-T治疗后复发的患者。

The field now stands at an inflection point at which therapeutic innovation is advancing faster than the evidence infrastructure required to guide practice.

目前该领域正处于一个转折点，治疗创新的步伐超过了指导实践所需的证据基础建设。

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.

实现持久且公平的益处将需要与当前CAR-T标准一致的对照组、协调一致的入选标准、前瞻性分子分型以及能够随着护理标准演变的自适应试验平台。

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.

随着ADCs和双特异性抗体在治疗中更早使用并广泛应用于社区实践，主要挑战已不再是开发有效的治疗手段，而是构建生物学上合理的、可获取的、可解释的治疗路径，使得对所有复发/难治性弥漫大B细胞淋巴瘤（R/R LBCL）患者来说，可耐受的、治愈性的治疗成为现实和普遍的目标。