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:High-risk multiple myeloma: how to treat at diagnosis and relapse?
High-risk multiple myeloma: how to treat at diagnosis and relapse?
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多发性骨髓瘤患者在过去一个世纪中生存率有了很大改善,这得益于新型治疗策略的引入。然而,一个预后比预期更差的亚组患者被认为是高危,其识别基于患者和疾病相关因素的存在,如衰弱、髓外疾病、细胞遗传学异常,甚至根据基线因素出现的比预期更早的复发。尽管高危特征患者的管理尚未很好确立,因为缺乏针对该亚组患者的具体试验以及他们在临床试验中代表性不足,但治疗应基于2个支柱进行规划:(1) 存在高危特征的较差预后至少可以通过实现深度且持续的缓解来改善甚至消除,(2) 这最可能通过使用最佳治疗选择并以响应适应的方式来实现。一些已规划或正在进行的临床试验仅纳入具有高危特征的患者,使用最有效的疗法(蛋白酶体抑制剂、免疫调节药物和抗CD38单克隆抗体)以及CAR-T 细胞和T细胞衔接器,这将揭示克服高危特征存在所致较差预后的最佳治疗 approach。
Patients with multiple myeloma have experienced a great improvement in survival over the past century because of the introduction of novel therapeutic strategies.
However, a subgroup of patients with poorer outcomes than expected is considered high risk and identified by the presence of patient- and disease-based factors such as frailty, extramedullary disease, cytogenetic abnormalities, or even relapses occurring earlier than expected according to the baseline factors. Although the management of patients with high-risk features is not well established because of the lack of specific trials in this subgroup of patients and because of their underrepresentation in the clinical trials, treatment should be planned on 2 pillars: (1) poor prognosis with the presence of high-risk features can be at least improved or even abrogated by achieving a deep and sustained response over time, and (2) this can most likely be obtained through using the best therapeutic options and in a response-adapted way.
Some clinical trials that have been planned or are ongoing include only patients with high-risk features, using the most effective therapies (proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies) as well as chimeric antigen receptor T cells and T-cell engagers that will unravel what the best therapeutic approach will be to overcome the poor prognosis of the presence of high-risk features.
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