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:Moving T-Cell Therapies into the Standard of Care for Patients with Relapsed or Refractory Follicular Lymphoma: A Review.
Moving T-Cell Therapies into the Standard of Care for Patients with Relapsed or Refractory Follicular Lymphoma: A Review.
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滤泡性淋巴瘤是一种惰性非霍奇金淋巴瘤,患者在其疾病进程中通常会经历多次复发。随着后续每一线治疗,缓解期逐渐缩短,临床结局逐渐恶化。目前,对于复发/难治性滤泡性淋巴瘤患者,尚无明确的标准治疗/首选治疗方案。随着新型药物不断涌现用于三线治疗,需要指导为每位患者选择最合适的治疗。基于在复发/难治性滤泡性淋巴瘤患者中的临床获益,已有几类靶向治疗药物获得监管机构批准,包括单克隆抗体、磷酸肌醇3-激酶抑制剂、zeste同源物2增强子抑制剂、嵌合抗原受体(CAR)T细胞疗法和双特异性抗体。
此外,抗体-药物偶联物和其他免疫细胞疗法正在该领域进行评估。在既往接受过两线或以上治疗后,将CAR-T 细胞疗法有效整合到治疗模式中,需要根据再次活检后的转化状态进行适当的患者选择;基于年龄、体能状态和缓解持续时间的风险评估;以及CAR-T 细胞疗法的合格性。考虑重要的后勤因素(例如,距离治疗中心的远近以及CAR-T 细胞治疗关键期间的照护者支持)也至关重要。
总体而言,对于复发/难治性滤泡性淋巴瘤患者,推荐采用个体化治疗方案,综合考虑患者相关因素(例如,年龄、疾病状态、肿瘤负荷、合并症)和既往治疗类型。需要进一步分析真实世界数据并更好地理解复发机制,以进一步完善患者选择并确定该背景下最佳的治疗顺序。
Patients with follicular lymphoma, an indolent form of non-Hodgkin lymphoma, typically experience multiple relapses over their disease course. Periods of remission become progressively shorter with worse clinical outcomes after each subsequent line of therapy. Currently, no clear standard of care/preferred treatment approach exists for patients with relapsed or refractory follicular lymphoma.
As novel agents continue to emerge for treatment in the third-line setting, guidance is needed for selecting the most appropriate therapy for each patient. Several classes of targeted therapeutic agents, including monoclonal antibodies, phosphoinositide 3-kinase inhibitors, enhancer of zeste homolog 2 inhibitors, chimeric antigen receptor (CAR) T-cell therapies, and bispecific antibodies, have been approved by regulatory authorities based on clinical benefit in patients with relapsed or refractory follicular lymphoma.
Additionally, antibody-drug conjugates and other immunocellular therapies are being evaluated in this setting. Effective integration of CAR-T cell therapy into the treatment paradigm after two or more prior therapies requires appropriate patient selection based on transformation status following a rebiopsy; a risk evaluation based on age, fitness, and remission length; and eligibility for CAR-T cell therapy.
Consideration of important logistical factors (e. g. , proximity to the treatment center and caregiver support during key periods of CAR-T cell therapy) is also critical.
Overall, an individualized treatment plan that considers patient-related factors (e. g. , age, disease status, tumor burden, comorbidities) and prior treatment types is recommended for patients with relapsed or refractory follicular lymphoma. Future analyses of real-world data and a better understanding of mechanisms of relapse are needed to further refine patient selection and identify optimal sequencing of therapies in this setting.
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