在复发性耐火多发性骨髓瘤中对达拉图巴基疗法的耐药性的基因组和免疫决定因素
Bachisio Ziccheddu1, Claudia Giannotta2, Mattia D'Agostino3
1Myeloma Division, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
Blood cancer journal
|July 19, 2024
概括
基因组复杂性和免疫变化导致复发性/耐药性多发性骨髓瘤 (RRMM) 中对达拉图巴基疗法的耐药性. 了解这些因素可以改善RRMM患者的治疗策略.
科学领域:
- 血液学 血液学 血液学
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
背景情况:
- 向免疫疗法,包括抗CD38单克隆抗体,如达拉图穆马布,可改善复发性/耐药性多发性髓瘤 (RRMM) 的无进展生存率.
- 尽管取得了进展,但很大一部分RRMM患者经历了疾病复发,需要对抗药机制有更深入的了解.
研究的目的:
- 调查导致RRMM患者耐药性的基因组和免疫因素,这些患者接受了达拉图姆巴,莱纳利多米德和德克萨米他松 (Dara-Rd) 治疗.
- 为了确定基因组驱动因素和免疫微环境变化,与Dara-Rd疗法下的早期进展相关.
主要方法:
- 在32名RRMM患者的全基因组测序 (WGS) 和流细胞测量的综合分析,这些患者接受了Dara-Rd.
- 纵向血液样本分析 (202个样本) 使用流细胞测量来跟踪免疫细胞的动态随时间推移.
- 对治疗前后样本进行基因组分析,以确定与进展相关的突变和结构变异.
主要成果:
- 全基因组测序确定了早期进展的基因组驱动因素,包括RPL5损失,APOBEC突变和MYC/染色体变异.
- 流细胞测量显示,在发病的患者中,有明显的免疫变化:CD38+NK细胞的枯竭,持续的T细胞枯竭和不充分的调节性T细胞减少.
- 在不良基因组特征和特定的免疫模式之间发现了关联,突出了它们在治疗耐药性的相互作用.
结论:
- 基因组复杂性和免疫微环境中的变化显著影响RRMM中对达拉图马布基调的耐药性.
- 达拉图穆马布诱导的免疫变化,加上特定的基因组变化,导致治疗失败.
- 综合基因组和免疫分析提供了对Dara-Rd耐药性机制的洞察力,可能指导未来的治疗策略.
更多相关视频
09:41An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
8.6K
09:34Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography
Published on: February 17, 2022
3.3K
相关概念视频
Treatment Resistant Cancers
3.3K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
Combination Therapies and Personalized Medicine
4.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K
Tumor Immunotherapy
504
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
504
