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:Minimal residual disease guided treatment approaches in non-Hodgkin lymphoma-Where we are and where we're headed.
Minimal residual disease guided treatment approaches in non-Hodgkin lymphoma-Where we are and where we're headed.
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微小残留病(MRD)评估,尤其是通过循环肿瘤DNA(ctDNA)进行检测,能够对B细胞非霍奇金淋巴瘤(NHL)各亚型的治疗反应提供高度肿瘤特异性和定量化的测量。传统影像学,包括正电子发射断层扫描(PET),仍然是NHL疗效评价标准的核心,但缺乏检测分子层面疾病的分析灵敏度。相比之下,超灵敏ctDNA可检测低至百万分之一的变异频率,并能在整个治疗过程中更精确地量化肿瘤负荷。在大型B细胞淋巴瘤中,ctDNA动力学在一线治疗后比PET更准确地预测临床结局,并在靶向药物和CAR-T 细胞治疗中保持预后价值。在套细胞淋巴瘤中,诱导治疗后MRD不可检出可识别出能够安全省略大剂量化疗巩固治疗的患者。目前,针对NHL各亚型的前瞻性临床试验常规纳入MRD评估,以检验其在临床决策中的效用,包括治疗时机和治疗选择。MRD在NHL中广泛应用的障碍包括缺乏标准化的标本采集和分析、检测可及性不足,以及缺乏明确证据表明治疗仅分子层面的疾病可改善结局。正在进行的临床试验正在填补这一信息空白,并将指导如何将MRD整合到常规临床诊疗中。
Minimal residual disease (MRD) assessment, particularly through circulating tumor DNA (ctDNA), offers highly tumor-specific and quantitative measurement of treatment response across subtypes of B-cell non-Hodgkin lymphoma (NHL). Conventional imaging, including positron emission tomography (PET) scans, remains central to the NHL response criteria but lacks the analytical sensitivity to detect molecular disease. In contrast, ultrasensitive ctDNA can detect variants at frequencies as low as 1 part per million and allows more precise quantification of tumor burden throughout therapy. In large B-cell lymphoma, ctDNA kinetics predict clinical outcomes more accurately after frontline therapy than PET and retain prognostic value with targeted agents and chimeric antigen receptor T-cell therapy.
In mantle cell lymphoma, undetectable MRD after induction identifies patients who can safely omit high-dose chemotherapy consolidation. Prospective clinical trials across NHL subtypes now routinely embed MRD assessment to test its utility in clinical decision-making, including timing and selection of therapy.
Barriers to widespread adoption of MRD in NHL include a lack of standardized specimen collection and analysis, assay availability, and definitive evidence that treating molecular-only disease improves outcomes. Ongoing clinical trials are addressing this information gap and will guide how MRD can be integrated into routine clinical care.
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