Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Curr Hematol Malig Rep. 2020 Feb;15(1):31-43. doi: 10.1007/s11899-020-00559-4.
Recent advances the genomic profiling of patients with Waldenström macroglobulinemia (WM) have led to the identification of novel therapeutic targets in these patients. In this review, we cover the current standard of care and the recently evaluated novel approaches with high potential to be incorporated in the therapeutic armamentarium against WM.
The MYD88 mutation is the most common genomic abnormality in WM, and is encountered in 80-95% of patients, making it an important target for drug development. The success of the first-generation Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has generated tremendous interest in the study of more selective and potent BTK inhibitors. Additionally, the identification of CXCR4 mutations in up to approximately 40% of patients with WM has fueled research regarding their implication on systemic therapy in WM. In a rapidly advancing field of targeted therapies, the treatment options for patients with WM are expanding as researchers continue to uncover and harness the survival pathways active in this hematologic malignancy.
最近对瓦尔登斯特伦巨球蛋白血症（WM）患者的基因组分析取得了进展，这为这些患者的新治疗靶点的确定提供了依据。在本综述中，我们讨论了目前的标准治疗方法，以及最近评估的具有很高潜力的新方法，这些新方法有可能被纳入 WM 的治疗武器库。
MYD88 突变是 WM 中最常见的基因组异常，发生在 80-95%的患者中，这使其成为药物开发的重要靶点。第一代 Bruton 酪氨酸激酶（BTK）抑制剂伊布替尼的成功极大地激发了人们对更具选择性和更强效 BTK 抑制剂的研究兴趣。此外，多达约 40%的 WM 患者存在 CXCR4 突变，这促使人们研究其对 WM 全身治疗的影响。在靶向治疗这一快速发展的领域，WM 患者的治疗选择正在扩大，因为研究人员继续发现并利用在这种血液恶性肿瘤中活跃的生存途径。
