1] Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL, USA [2] Department of Oncologic Sciences, H. Lee Moffitt Cancer Center, University of South Florida College of Medicine, Tampa, FL, USA.
Department of Leukemia, MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
Leukemia. 2014 Mar;28(3):507-17. doi: 10.1038/leu.2013.311. Epub 2013 Oct 25.
Understanding the pathogenesis of CLL has uncovered a plethora of novel targets for human application of monoclonal antibodies, engineered T cells, or inhibitors of signal transduction pathways. The B-cell receptor signaling pathway is being actively explored as a therapeutic target in CLL. Ibrutinib, an inhibitor of Bruton's tyrosine kinase is showing impressive responses in heavily pre-treated high-risk CLL, whether alone or in combination with MoAbs or chemotherapy. Other key components of the BCR pathway, namely PI3K-δ, are also being targeted with novel therapies with promising results as well. Future trials would likely evaluate ibrutinib in the front-line setting. Moreover, improvements in allogeneic HCT mostly by continuing to reduce associated toxicity as well as incorporating cellular therapies such as autologous CLL tumor vaccines, among others, will continue to expand. This is also the case for the next generation of chimeric antigen receptor therapy for CLL once genetically modified T cells are available at broad scale and with improved efficacy. As our ability to further refine and integrate these therapies continues to improve, and we gain further knowledge from gene sequencing, we anticipate that treatment algorithms will continue to be revised to a more personalized approach to treat this disease with improved efficacy and devoid of unnecessary toxicity.
了解 CLL 的发病机制揭示了许多新的靶点，可用于人类应用单克隆抗体、工程 T 细胞或信号转导途径抑制剂。B 细胞受体信号通路作为 CLL 的治疗靶点正在被积极探索。伊布替尼是一种布鲁顿酪氨酸激酶抑制剂，在未经预处理的高危 CLL 中，无论是单独使用还是与 MoAb 或化疗联合使用，都显示出令人印象深刻的反应。BCR 通路的其他关键成分，即 PI3K-δ，也正在用新型疗法进行靶向治疗，也取得了很好的效果。未来的试验可能会评估伊布替尼在一线治疗中的作用。此外，同种异体 HCT 的改进主要通过继续降低相关毒性，以及纳入细胞疗法，如自体 CLL 肿瘤疫苗等，将继续扩大。对于下一代用于 CLL 的嵌合抗原受体疗法也是如此，一旦基因修饰的 T 细胞可以广泛获得并具有更高的疗效。随着我们进一步完善和整合这些疗法的能力不断提高，以及我们从基因测序中获得更多的知识，我们预计治疗算法将继续修订为更个性化的方法，以提高疗效，避免不必要的毒性来治疗这种疾病。
