低频PPM1D基因突变影响治疗对CD19向CAR T细胞治疗的大B细胞淋巴瘤的治疗反应
Katja Seipel1,2, Michèle Frey2, Henning Nilius3
1Department for Biomedical Research (DBMR), University of Bern, 3008 Bern, Switzerland.
Current oncology (Toronto, Ont.)
|December 22, 2023
概括
PPM1D基因的突变在克隆性血液形成中很常见,并且可能预测在接受CAR T细胞治疗的复发性或耐火性扩散性大B细胞淋巴瘤患者的结果会更差.
科学领域:
- 血液学 血液学 血液学
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
背景情况:
- 化学抗原受体T (CAR T) 细胞疗法是复发或耐火性扩散大B细胞淋巴瘤 (r/r DLBCL) 的标准治疗方法.
- 在克隆性血液形成 (CH) 中常见的PPM1D基因突变,赋予PPM1D/Wip1酸酶功能获取活性,可能影响细胞增殖和治疗反应.
- 之前的研究表明,PPM1D突变与淋巴瘤患者标准化疗效率降低相关.
研究的目的:
- 研究低频PPM1D突变对针对CD19的CAR T细胞治疗在r/rDLBCL患者的安全性和有效性的影响.
- 评估PPM1D突变状态与临床结果之间的相关性,包括细胞因子释放综合征 (CRS),免疫效应细胞相关的神经毒性 (ICANS),无进展生存率 (PFS) 和整体生存率 (OS).
主要方法:
- 分析了一组85名r/r DLBCL患者的队列,这些患者接受了针对CD19的CAR T细胞治疗.
- 使用分子分析评估PPM1D基因突变流行率和变异性等位基因频率 (VAF).
- 在具有和没有PPM1D突变的患者之间比较安全性 (CRS,ICANS) 和疗效 (缓解率,PFS,OS).
主要成果:
- 在20%的患者队列中存在PPM1D突变,平均VAF为0.052.
- 在PPM1D突变和野生型子组中,CAR T细胞治疗的安全概况 (CRS和ICANS发病率) 类似.
- 患有PPM1D突变的患者表现出更糟糕的临床结果,包括较低的完全缓解率 (56%在野生类型相比60%在突变型中的部分缓解),较短的PFS中位数 (3vs12个月) 和显著减少的中位数OS (5vs37个月).
结论:
- 在CH的背景下,低频PPM1D突变似乎不会影响针对CD19的CAR T细胞治疗的安全性.
- 在接受CAR T细胞治疗的r/r DLBCL患者中,PPM1D突变与较差的临床结果有关,包括无进展和整体存活率.
- 在接受CAR T细胞治疗的r/r DLBCL患者中,PPM1D突变状态可以作为治疗反应和生存的预测生物标志物.
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