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:Multiple myeloma.
Multiple myeloma.
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多发性骨髓瘤(MM)是一种涉及肿瘤性浆细胞的血液淋巴系统恶性肿瘤,通常以存在单克隆免疫球蛋白为特征。MM是第二常见的血液系统恶性肿瘤,全球发病率不断上升。由于大多数患者会复发或对治疗产生难治性,该病仍无法治愈。MM是一种遗传学复杂的疾病,具有高度异质性,其发展是一个多步骤过程,涉及肿瘤细胞遗传学改变的获得以及骨髓微环境的变化。症状性MM的诊断依据国际骨髓瘤工作组标准,即骨髓浸润≥10%克隆性浆细胞,并存在至少一项骨髓瘤定义事件, either 标准CRAB特征(高钙血症、肾功能衰竭、贫血和/或溶骨性骨病变)或即将发生器官损害的生物学标志物。年轻且体能状态良好的患者被认为适合移植。他们接受诱导治疗,随后接受大剂量美法仑联合自体造血细胞移植的巩固治疗,以及维持治疗。在老年成人中(不适合移植),达雷妥尤单抗、来那度胺和地塞米松联合方案是首选。如果发生复发并需要进一步治疗,治疗选择将基于既往治疗及疗效,目前包括免疫疗法,如双特异性单克隆抗体和CAR-T 细胞疗法。
Multiple myeloma (MM) is a haematological lymphoid malignancy involving tumoural plasma cells and is usually characterized by the presence of a monoclonal immunoglobulin protein. MM is the second most common haematological malignancy, with an increasing global incidence. It remains incurable because most patients relapse or become refractory to treatments. MM is a genetically complex disease with high heterogeneity that develops as a multistep process, involving acquisition of genetic alterations in the tumour cells and changes in the bone marrow microenvironment. Symptomatic MM is diagnosed using the International Myeloma Working Group criteria as a bone marrow infiltration of ≥10% clonal plasma cells, and the presence of at least one myeloma-defining event, either standard CRAB features (hypercalcaemia, renal failure, anaemia and/or lytic bone lesions) or biomarkers of imminent organ damage.
Younger and fit patients are considered eligible for transplant. They receive an induction, followed by consolidation with high-dose melphalan and autologous haematopoietic cell transplantation, and maintenance therapy. In older adults (ineligible for transplant), the combination of daratumumab, lenalidomide and dexamethasone is the preferred option.
If relapse occurs and requires further therapy, the choice of therapy will be based on previous treatment and response and now includes immunotherapies, such as bi-specific monoclonal antibodies and chimeric antigen receptor T cell therapy.
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