决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Therapeutic Horizon in Multiple Myeloma: Analysis of the Emerging Landscape of Clinical Trials.
多发性骨髓瘤临床试验的增加凸显了向生物治疗的转变,尤其是免疫治疗和 CAR-T 等基因治疗。
背景:多发性骨髓瘤(MM)的新兴疗法显著改善了患者结局、延长生存,并推动治疗向更具靶向性、疗效更高且毒性更低的方向发展。然而,该病仍无法治愈。 目的:通过评估 2014 至 2024 年临床试验中的候选药物,分析 MM 的治疗格局。 方法:数据来自 ClinicalTrials.gov(CTG)和 Cortellis Drug Discovery Intelligence(CDDI),包括针对新诊断及难治性 MM、有结果报告的活跃和已完成研究。采用 Joinpoint 回归模型估算年度百分比变化(APC)和平均年度百分比变化(AAPC)。按临床试验特征、靶向策略及其对治疗进展的潜在影响分析数据。 结果:研究筛查了 CDDI 的 1,091 项试验和 CTG 的 1,947 项试验,最终纳入 365 项进行详细分析。I 期试验最常见(n=182;49.9%);研究中的疗法以生物制剂为主(n=251;68.8%)。干预类型中,细胞疗法占主导(n=171;46.8%);近年来研究最多的 CAR-T 产品靶向 BCMA(n=107)、CD19(n=16)和 GPRC5D。转折点之前,活跃试验数每年增长 1.86%(95% CI:1.67–2.06),相当于每年平均增加 11.9 项;转折点之后,增长加快至每年 3.69%(95% CI:3.19–4.19),相当于每年增加 26.5 项。整个研究期间的加权平均年度百分比变化(AAPC)为 2.63%。 结论:MM 临床试验数量增加,反映治疗正转向生物疗法,尤其是 CAR-T 等免疫疗法和基因疗法。
BACKGROUND: Emerging therapies for multiple myeloma (MM) have significantly improved patient outcomes extending survival and advancing treatment toward more targeted, effective, and less toxic approaches. However, the disease remains incurable. OBJECTIVES: Analyze the therapeutic landscape of MM by evaluating drug candidates in clinical trials from 2014 to 2024. METHODS: Data were extracted from ClinicalTrials.gov (CTG) and Cortellis Drug Discovery Intelligence (CDDI), including active and completed studies with results on newly diagnosed and refractory MM. Joinpoint regression models estimated Annual Percent Changes (APCs) and Average Annual Percent Changes (AAPC). Data were examined by clinical trial characteristics, targeting strategies, and potential impact on treatment advancements. RESULTS: A total of 1091 trials from CDDI and 1947 from CTG were screened, yielding 365 studies eligible for detailed analysis. Phase I trials were the most common (n = 182; 49.9%), and biologic agents represented the majority of the investigational therapies (n = 251; 68.8%). Among intervention types, cell therapies were predominant (n = 171; 46.8%), with CAR-T products targeting BCMA (n = 107), CD19 (n = 16), and GPRC5D (n = 12) emerging as the most studied in recent years. Before the joinpoint, the number of active trials grew by 1.86% per year (95% CI: 1.67-2.06), corresponding to an average increase of 11.9 studies annually. After the joinpoint, growth accelerated to 3.69% per year (95% CI: 3.19-4.19), equivalent to 26.5 additional trials each year. Across the entire study period, the weighted average annual percentage change (AAPC) was 2.63%. CONCLUSION: The rise in MM clinical trials highlights a shift toward biologic therapies, particularly immunotherapies and gene therapies like CAR-T.
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