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:Will immunotherapy lead to a breakthrough in the treatment of older adults with ALL?
Will immunotherapy lead to a breakthrough in the treatment of older adults with ALL?
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
传统上,化疗治疗的老年B细胞急性淋巴细胞白血病(ALL)患者结局不佳。因此,迫切需要创新方法改善这一人群的结局。靶向CD19的免疫疗法,如blinatumomab和嵌合抗原受体(CAR)T细胞疗法,在复发/难治性(r/r)B细胞ALL中取得了显著应答,包括清除微小残留病灶(MRD)。现有数据支持blinatumomab用于晚期老年B细胞ALL患者具有疗效和安全性。
因此,其应用正扩展至B细胞ALL一线方案,特别是老年患者。目前有多项研究积极评估blinatumomab单药或与减量传统化疗、新型药物联合用于新诊断老年ALL患者,早期数据令人鼓舞。靶向CD19的CAR(CD19CAR)T细胞疗法对复发/难治性B细胞ALL儿童和年轻成人有效,但支持其用于老年ALL患者疗效和安全性的数据稀少。
此外,FDA已商业批准的r/r ALL CD19CAR-T 细胞产品仅适用于25岁以下患者。尽管担忧老年患者可能无法耐受CAR-T 细胞治疗的预期毒性(这些毒性可能危及生命),但针对性预防和早期干预措施联合更安全的CAR-T 细胞平台,或可提高耐受性并进一步将这种有前景的疗法扩展至老年ALL患者。本文综述老年B细胞ALL免疫疗法的进展,以及其改变新诊断患者一线治疗的潜力。
Historically, older adults with B-cell acute lymphoblastic leukemia (ALL) have done poorly with chemotherapy-based treatment.
Therefore, new innovative approaches are urgently needed to improve outcomes for this population. CD19-targeted immunotherapies such as blinatumomab and chimeric antigen receptor (CAR) T cell therapy have produced remarkable responses in relapsed/refractory (r/r) B-cell ALL, including clearance of minimal residual disease (MRD). Available data support the efficacy and safety of blinatumomab in older adults with advanced B-cell ALL.
Therefore, its application is being extended to frontline regimens for B-cell ALL, particularly in older adults. There are several studies actively examining the role of blinatumomab alone or in combination with attenuated dosing of conventional chemotherapy or novel agents in older adults with newly diagnosed ALL and early data are encouraging. While CD19-targeted CAR (CD19CAR) T cell therapy is active in children and young adults with r/r B-cell ALL, data supporting its efficacy and safety in older adults with ALL is scarce.
Furthermore, the commercially FDA approved CD19CAR T cell therapy product for r/r ALL is restricted only to patients 25 years of age. Although there are concerns about older adults tolerating the expected toxicities associated with CAR T cell therapy, which may be life threatening, tailored approaches for prophylactic and pre-emptive interventions combined with utilization of safer CAR T cell platforms may improve tolerability and further extend the use of this promising treatment to older patients with ALL.
In this review, we will discuss the progress in immunotherapies for older adults with B-cell ALL and their potential for transforming frontline therapy for newly diagnosed patients.
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