Kasi Pashtoon Murtaza, Ansell Stephen M, Gertz Morie A
Mayo Clinic, Rochester, MN.
Clin Adv Hematol Oncol. 2015 Jan;13(1):56-66.
Waldenström macroglobulinemia (WM) is an indolent low-grade lymphoma characterized by bone marrow infiltration with lymphoplasmacytic cells associated with a monoclonal immunoglobulin M protein. It is considered incurable. The 5-year survival rate for patients with symptomatic WM is 87% for those with low-risk disease, 68% for those with intermediate-risk disease, and 36% for those with high-risk disease. Owing to recent advances in therapy with new targeted treatment options, relative survival has improved. Insights into mutations in MYD88 L265P and the WHIM-like CXCR4 have been shown to be significant not just in terms of their diagnostic and prognostic value, but also as potential targets for therapy. For patients with symptomatic WM, the different classes of agents used to treat WM include alkylating agents (eg, cyclophosphamide and chlorambucil), nucleoside analogues (eg, cladribine and fludarabine) and monoclonal antibodies (eg, rituximab and alemtuzumab). With an increasing number of novel treatment options available including everolimus, bendamustine, bortezomib, ibrutinib, carfilzomib, lenalidomide, and panobinostat, the optimal timing and introduction of these options in the absence of phase 3 trials remains controversial. A treatment algorithm based on Mayo Stratification for Macroglobulinemia and Risk-Adapted Therapy (mSMART) and a comparison of important clinical trials in WM is provided.
华氏巨球蛋白血症（WM）是一种惰性低度淋巴瘤，其特征是骨髓被淋巴浆细胞浸润，并伴有单克隆免疫球蛋白M蛋白。它被认为是无法治愈的。有症状的WM患者中，低风险疾病患者的5年生存率为87%，中风险疾病患者为68%，高风险疾病患者为36%。由于新的靶向治疗方法在治疗方面的最新进展，相对生存率有所提高。对MYD88 L265P和WHIM样CXCR4突变的深入了解不仅在诊断和预后价值方面具有重要意义，而且作为潜在的治疗靶点也具有重要意义。对于有症状的WM患者，用于治疗WM的不同类别的药物包括烷化剂（如环磷酰胺和苯丁酸氮芥）、核苷类似物（如克拉屈滨和氟达拉滨）和单克隆抗体（如利妥昔单抗和阿仑单抗）。随着越来越多的新型治疗选择出现，包括依维莫司、苯达莫司汀、硼替佐米、伊布替尼、卡非佐米、来那度胺和帕比司他，在缺乏3期试验的情况下，这些选择的最佳使用时机仍存在争议。本文提供了基于梅奥巨球蛋白血症分层和风险适应性治疗（mSMART）的治疗算法以及WM重要临床试验的比较。
