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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Early Relapse in First-Line Follicular Lymphoma: A Review of the Clinical Implications and Available Mitigation and Management Strategies.
Early Relapse in First-Line Follicular Lymphoma: A Review of the Clinical Implications and Available Mitigation and Management Strategies.
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对于既往未经治疗、具有症状或肿瘤负荷较高的滤泡性淋巴瘤患者,利妥昔单抗联合化疗(R-chemo)或奥妥珠单抗联合化疗(G-chemo)是标准治疗。R-chemo后继续利妥昔单抗维持治疗的中位无进展生存期(PFS)超过10年;与相应的含利妥昔单抗方案相比,G-chemo后继续奥妥珠单抗维持治疗可改善PFS。尽管疗效积极,仍有相当一部分患者在初始治疗期间或治疗后不久出现疾病进展。早期复发尚无统一定义,但初始治疗后24个月内疾病进展(POD24)已被广泛认可为重要的不良预后因素。多项研究显示,与未发生POD24者相比,发生POD24的患者死亡风险更高。遗憾的是,目前评估POD24风险的工具仍不理想,临床实践中尚无法准确识别哪些个体患者早期复发风险较高。针对POD24患者的治疗策略也尚未明确。与R-chemo相比,G-chemo似乎可降低POD24风险,但其对生存结局的影响仍不清楚。除标准治疗外,自体干细胞移植以及双特异性抗体、CAR-T 细胞等新兴疗法,未来可能在治疗中发挥作用。在标准方案尚未确立之前,采用有效的一线治疗降低早期复发风险仍是当前重点。
Chemoimmunotherapy with rituximab (R-chemo) or obinutuzumab (G-chemo) is standard of care for patients with previously untreated symptomatic or high-tumor-burden follicular lymphoma. Median progression-free survival (PFS) with R-chemo plus R maintenance exceeds 10 years, and G-chemo plus G maintenance improves PFS relative to the corresponding R-containing regimen. Despite these positive results, a sizable proportion of patients continue to progress during or shortly after initial treatment. While no single definition of early relapse has been established, progression of disease within 24 months of initial treatment (POD24) is now widely accepted as a critical adverse prognostic factor. Multiple studies have shown increased mortality risk in patients with POD24 versus those without POD24.
Unfortunately, tools for the assessment of POD24 risk are suboptimal, and it is not currently possible in clinical practice to identify individual patients who are at increased risk for early relapse. Treatment strategies for patients with POD24 are not well defined. G-chemo regimens appear to reduce the risk of POD24 relative to R-chemo regimens, although the impact on survival outcomes remains unclear.
Beyond standard therapy, autologous stem cell transplant and emerging treatment modalities, such as bispecific antibodies and chimeric antigen receptor T-cells, may have a role in future management. Until standard treatments are defined, mitigating the risk of early relapse with effective up-front treatment remains the priority.
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