决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
英文原题:Follicular Lymphoma: Novel Therapies and Strategies for Optimal Therapeutic Sequencing.
Follicular Lymphoma: Novel Therapies and Strategies for Optimal Therapeutic Sequencing.
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滤泡性淋巴瘤(FL)是最常见的惰性非霍奇金淋巴瘤,其特征为反复复发与缓解的病程,在现代治疗下中位总生存期超过15-20年。尽管化学免疫治疗仍是前线管理的基石,但双特异性抗体、CAR-T 细胞产品及抗体药物偶联物等新型药物的快速获批,已从根本上重塑了复发/难治(R/R)阶段的治疗格局。本综述总结了治疗全程的当前证据,并提出了一套实用的、风险适应的序贯治疗框架。
双特异性抗体(mosunetuzumab、epcoritamab)在重度经治FL中已显示出持久的完全缓解,且毒性特征可控。CAR-T 细胞疗法(axicabtagene ciloleucel、lisocabtagene maraleucel和tisagenlecleucel)已获批用于既往接受过两线或以上治疗的R/R FL,尽管存在显著的物流和安全方面的考量,但仍可提供高缓解率。纳入来那度胺-利妥昔单抗的一线试验已确立了无化疗方案,其长期结局与化学免疫治疗相当。抗体-药物偶联物和双特异性抗体联合治疗的新兴数据持续拓展治疗手段。尽管许多FL患者可获得良好的长期结局,但复发仍然常见,且随着治疗线数增加,缓解持续时间通常缩短。越来越多具有不同作用机制的有效药物既带来了机遇,也增加了复杂性。基于证据的序贯治疗策略——需考虑既往治疗暴露、患者体能状态及机制特异性因素——对于在整个疾病轨迹中最大化结局日益关键。
PURPOSE OF REVIEW: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, characterized by a relapsing and remitting course and a median overall survival exceeding 15-20 years with modern therapy. While chemoimmunotherapy remains the cornerstone of frontline management, the rapid approval of novel agents, including bispecific antibodies, CAR T-cell products, and antibody-drug conjugates, has fundamentally reshaped the relapsed/refractory (R/R) landscape. This review summarizes current evidence across the treatment continuum and propose a practical, risk-adapted sequencing framework. RECENT FINDINGS: Bispecific antibodies (mosunetuzumab, epcoritamab) have demonstrated durable complete responses in heavily pretreated FL, with manageable toxicity profiles.
CAR T-cell therapy (axicabtagene ciloleucel, lisocabtagene maraleucel, and tisagenlecleucel) are approved in R/R FL after two or more prior lines, offering high response rates albeit notable logistal and safety considerations. Frontline trials incorporating lenalidomide-rituximab have established chemotherapy-free option with long-term outcomes comparable to chemoimmunotherapy. Emerging data on antibody-drug conjugates and bispecific antibody combination therapy continue to expand the therapeutic arsenal.
Despite favorable long-term outcomes for many patients with FL, relapse remains common and remission typically shortens with successive lines of therapy. The growing number of effective agents with distinct mechanisms of action creates both opportunity and complexity. Evidence-based sequencing strategies that account for prior therapy exposure, patient fitness and mechanism-specific considerations are increasingly critical to maximizing outcomes across the disease trajectory.
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