Department of Hematologic Oncology, Massachusetts General Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Leuk Lymphoma. 2021 Aug;62(8):1805-1815. doi: 10.1080/10428194.2021.1881514. Epub 2021 Feb 11.
Waldenström Macroglobulinemia (WM) is an incurable hematologic malignancy characterized by lymphoplasmacytic infiltration of the bone marrow and the presence of monoclonal immunoglobulin (IgM). Although a portion of WM patients may experience a relatively indolent course, patients may experience IgM-related morbidity and/or disease-related mortality. This underscores the need for novel approaches to improve response and survival rates. Significant progress had been made in our understanding of the genomics and biology of WM. The discovery of the highly recurrent somatic mutations in the gene detected in 90-95% and the gene detected in 30-40% of WM patients has provided an opportunity to develop novel targeted approaches. Mutational status has important implications in predicting response to therapies such as BTK inhibitors. Treatment of WM should be guided by many factors including performance status, comorbidities, goals of therapy, and toxicities. In this review, we describe how current genomics may be utilized to optimize WM treatment selection. As the therapeutic landscape of WM continues to expand with more targeted approaches, the genomics in WM will likely play a greater role in individualizing treatment.
华氏巨球蛋白血症（WM）是一种不可治愈的血液恶性肿瘤，其特征是骨髓中淋巴浆细胞浸润和单克隆免疫球蛋白（IgM）的存在。尽管一部分 WM 患者可能经历相对惰性的病程，但患者可能会出现 IgM 相关的发病率和/或疾病相关的死亡率。这凸显了需要新的方法来提高缓解率和生存率。我们在理解 WM 的基因组学和生物学方面取得了重大进展。在 90-95%的 WM 患者中检测到高度反复出现的 基因突变，在 30-40%的 WM 患者中检测到 基因突变，这为开发新的靶向方法提供了机会。突变状态对预测 BTK 抑制剂等治疗的反应具有重要意义。WM 的治疗应根据多种因素进行指导，包括身体状况、合并症、治疗目标和毒性。在这篇综述中，我们描述了如何利用当前的基因组学来优化 WM 的治疗选择。随着 WM 的治疗领域随着更多靶向方法的不断扩展，WM 的基因组学可能在个体化治疗中发挥更大的作用。
