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:How First-Line Therapy is Changing in non-Transplant Eligible Multiple Myeloma Patients.
How First-Line Therapy is Changing in non-Transplant Eligible Multiple Myeloma Patients.
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近几十年来,由于对多发性骨髓瘤生物学的新认识以及新药和治疗方法的引入,多发性骨髓瘤患者的治疗结局有所改善。超过一半的多发性骨髓瘤患者不适合移植,多年来,由于该患者群体的异质性以及缺乏治疗选择,其治疗一直很困难。近年来,人们关注衰弱的概念及其量化,以便根据体能状态调整治疗方案和剂量。针对衰弱的治疗调整可以减少副作用和毒性相关死亡,并界定不同的治疗成功。衰弱的作用以及新工具的开发可能为不适合移植的不同多发性骨髓瘤患者的个体化治疗提供前进方向。新联合方案的使用,特别是基于抗 CD38 单克隆抗体的方案,在 PFS 和 OS 方面显示出深远而持久的结果。如今,这些联合方案,尤其是 daratumumab-lenalidomide 和 dexamethasone,代表了这些患者治疗的“金标准”。最新的四联疗法和细胞导向疗法,包括双特异性抗体和CAR-T 细胞治疗,似乎非常有效,并可实现高比例的微小残留病阴性。后述这些方法可能重新定义目前被认为适合移植的 65 岁以上人群。
Treatment outcomes for patients with multiple myeloma have improved in recent decades thanks to new insights into the biology of the disease and the introduction of new drugs and therapeutic approaches. More than half of patients with multiple myeloma are not eligible for transplantation, and for years, their treatment has been difficult due to the heterogeneity of this patient group and the lack of treatment options. Recently, attention has focused on the concept of frailty and its quantification in order to adapt the schedule and dosage of treatment to the state of fitness. Modulation of therapy for frailty can reduce side effects and toxicity-related death and define the various successes of therapy.
The role of frailty and the development of new tools may provide a way forward to customize the treatment of different patients with multiple myeloma who are not eligible for transplantation. The use of the new association, particularly based on monoclonal antibodies against CD38, showed profound and durable results in terms of progression-free survival and overall survival.
Today, these combinations, especially daratumumab-lenalidomide and dexamethasone, represent the "gold standard" of treatment for these patients. The latest quadruplet therapies and cell-directed therapies, including bispecific antibodies and chimeric antigen receptor T-cell (CAR-T) treatment, appear to be very effective and achieve a high rate of negative minimal residual disease. These latter approaches could redefine the population over the age of 65 that is now considered transplant-eligible.
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