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:Considerations for the treatment of older adults with chronic lymphocytic leukemia.
Considerations for the treatment of older adults with chronic lymphocytic leukemia.
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尽管现代疗法在提高耐受性的同时带来了更长的生存期,但仍有若干争议尚存。
引言:慢性淋巴细胞白血病(CLL)主要影响老年人,确诊中位年龄约70岁。尽管靶向治疗改善了结局,但老年患者的治疗决策仍受到合并症、衰弱以及临床试验代表性不足等因素影响。综述内容:本综述将老年肿瘤学原则与治疗证据相结合,为老年CLL患者管理提供指导。文章总结初治及复发/难治性治疗策略,依据重要临床试验和真实世界研究,并纳入衰弱评估、多重用药、心血管风险及支持治疗方面的共识。讨论新型药物和治疗方法时,结合患者功能状态、偏好及生活质量,提出以年龄适配为导向的实用框架,这是既往综述未涉及的内容。专家观点:现代疗法虽可延长生存并提高耐受性,但仍有若干争议。一项挑战是如何管理体能处于临界状态的患者:他们尚未达到正式衰弱标准,却有显著合并症或器官功能障碍。另一挑战是在患者无法耐受或疾病进展后,如何安排BTK和BCL2抑制剂之后的治疗顺序,目前证据有限。非共价BTK抑制剂、双特异性抗体和CAR-T 等新兴选择显示出潜力,但其在老年或衰弱患者中的作用尚不明确。未来需要开展年龄适配型试验并采用生物标志物驱动策略,在延长生存的同时兼顾生活质量。
INTRODUCTION: Chronic lymphocytic leukemia (CLL) primarily affects older adults, with a median age at diagnosis around 70 years. While targeted therapies have improved outcomes, treatment decisions in the elderly are complicated by comorbidities, fraility, and underrepresentation in clinical trials. AREAS COVERED: This review integrates geriatric oncology principles with therapeutic evidence to guide management of older adults with CLL. It summarizes frontline and relapsed/refractory strategies, drawing from landmark trials and real-world studies, and incorporates consensus on frailty assessment, polypharmacy, cardiovascular risk, and supportive care.
Novel agents and treatment approaches are discussed in the context of functional status, patient preference, and quality of life, offering a practical age-adapted framework not addressed in prior reviews. EXPERT OPINION: While modern therapies allow longer survival with improved tolerability, several controversies remain. One challenge is managing patients with borderline fitness - those not formally frail yet with significant comorbidities or organ dysfunction.
Another is sequencing after intolerance or progression on both BTK and BCL2 inhibitors, where evidence is sparse. Emerging options such as non-covalent BTK inhibitors, bispecific antibodies, and CAR-T hold promise, but their role in older or frail patients is unclear. Future age-adapted trials and biomarker-driven strategies are needed to balance survival with quality of life.
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