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:Is There a Role for Daratumumab Retreatment in Patients with Relapsed/Refractory Multiple Myeloma?
Is There a Role for Daratumumab Retreatment in Patients with Relapsed/Refractory Multiple Myeloma?
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多发性骨髓瘤(MM)是一种血液系统疾病,其特征是恶性浆细胞克隆性扩增并在骨髓中积聚,导致溶骨性骨病、高钙血症、贫血和肾功能不全。Daratumumab 是首个获批用于治疗 MM 的抗 CD38 单克隆抗体,最初用于复发/难治性环境,最近也用于新诊断患者。Daratumumab 一线使用增加也将实质性改变复发/难治性疾病患者的治疗方式。由于双特异性 T 细胞重定向抗体(BsAbs)和CAR-T 细胞疗法(CAR-T)在许多国家真实环境中的成本和可及性,后续治疗线中再次使用 daratumumab 可能是一个合理选择。关于 daratumumab 再治疗疗效和最佳联合方案的数据缺乏,在此我们对现有数据进行简要文献综述。
我们仅识别出少量基于真实环境中病历回顾性分析的文章。在主要为重度经治的 MM 患者中,注意到缓解率和治疗持续时间结果具有高度一致性,约一半患者在基于 daratumumab 的方案再治疗后达到至少部分缓解(PR)。再治疗阶段的治疗持续时间和至下一次治疗时间相当长,并与后线治疗的临床预期一致。本文献综述中的数据分析表明,尽管既往暴露过 daratumumab,daratumumab 再治疗仍可能为部分复发/难治性 MM 患者提供有意义的临床获益。
然而,仍需进一步研究以识别可预测 daratumumab 再治疗良好反应的临床和生物学参数。
Multiple myeloma (MM) is a hematologic disease characterized by the clonal expansion of malignant plasma cells that accumulate in the bone marrow, leading to osteolytic bone disease, hypercalcemia, anemia, and renal dysfunction. Daratumumab was the first monoclonal anti-CD38 antibody approved for the treatment of MM, initially in relapse/refractory settings and, more recently, for newly diagnosed patients. Increased first-line usage of daratumumab will also substantially change treatment approaches for patients with relapsed/refractory disease.
Due to the cost and availability of bispecific T cell redirecting antibodies (BsAbs) and chimeric antigen receptor T cell therapy (CAR-T) in real-life settings in many countries, retreatment with daratumumab in subsequent lines of therapy might be a reasonable choice. Data regarding efficacy and optimal combinations of daratumumab retreatment are lacking, and here we provide a short literature review of available data.
We identified only a small number of articles based on retrospective analysis of medical records in real-life settings. A strong consistency in results regarding response rates and treatment duration was noticed among mainly heavily pre-treated MM patients, with approximately half of patients achieving at least partial remission (PR) after retreatment with daratumumab-based protocol.
The duration of treatment and time to the next treatment for retreatment episodes were considerable and consistent with clinical expectations for later lines of therapy. The analysis of data in this literature review indicates that daratumumab retreatment may provide meaningful clinical benefit to some patients with relapsed/refractory MM despite having prior exposure.
However, further research is needed to identify clinical and biological parameters that may predict favorable responses to daratumumab retreatment.
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