第11届瓦尔登斯特罗姆巨球蛋白血症国际研讨会（IWWM-11）达成共识的第1个专家组（CP1）负责更新治疗WM有症状、初诊病人的指南。该组强调，对于无症状且免疫球蛋白M没有显著升高或造血功能未受损害的病人，观察等待仍是黄金标准。对于一线治疗，化疗免疫疗法（CIT）方案，如地塞米松、环磷酰胺、利妥昔单抗（DRC）或苯达莫司汀、利妥昔单抗（Benda-R）仍然在WM治疗中扮演核心角色，因为它们有效、疗程固定、耐受性良好且费用适中。共价BTK抑制剂（cBTKi）为WM患者的一线治疗提供了一种连续性良好的替代方案，尤其对于那些不适合CIT的患者。在IWWM-11更新的III期随机试验中，二代cBTKi扎努布替尼的毒性比伊布替尼小，并引起更深的缓解，因此将扎努布替尼归类为WM的适当治疗选择。尽可能在治疗开始时确定MYD88和CXCR4的突变状态，因为这两个基因的改变预示着对于cBTKi的敏感性。治疗WM相关的冷球蛋白血症、冷凝集素、AL淀粉样变性、Bing-Neel综合症（BNS）、周围神经病和高黏滞综合征的方法遵循减少肿瘤和异常蛋白负荷的共同原则，从而改善症状。在BNS中，伊布替尼可能高度活跃并产生持久的缓解。相反，不建议使用cBTKi治疗AL淀粉样变性。该组强调，持续改善治疗有症状的初诊WM患者的选择取决于患者在临床试验中的参与，尽可能参与临床试验。版权所有 © 2023. Elsevier Inc. 发布

Consensus Panel 1 (CP1) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11) was tasked with updating guidelines for the management of symptomatic, treatment-naïve patients with WM. The panel reiterated that watchful waiting remains the gold standard for asymptomatic patients without critically elevated IgM or compromised hematopoietic function. For first-line treatment, chemoimmunotherapy (CIT) regimens such as dexamethasone, cyclophosphamide, rituximab (DRC), or bendamustine, rituximab (Benda-R) continue to play a central role in managing WM, as they are effective, of fixed duration, generally well-tolerated, and affordable. Covalent BTK inhibitors (cBTKi) offer a continuous, generally well-tolerated alternative for the primary treatment of WM patients, particularly those unsuitable for CIT. In a Phase III randomized trial updated at IWWM-11, the second-generation cBTKi, zanubrutinib, was less toxic than ibrutinib and induced deeper remissions, thus categorizing zanubrutinib as a suitable treatment option in WM. While the overall findings of a prospective, randomized trial updated at IWWM-11 did not show superiority of fixed duration rituximab maintenance over observation following attainment of a major response to Benda-R induction, a subset analysis showed benefit in patients >65 years and those with a high IPPSWM score. Whenever possible, the mutational status of MYD88 and CXCR4 should be determined before treatment initiation, as alterations in these 2 genes predict sensitivity towards cBTKi activity. Treatment approaches for WM-associated cryoglobulins, cold agglutinins, AL amyloidosis, Bing-Neel syndrome (BNS), peripheral neuropathy, and hyperviscosity syndrome follow the common principle of reducing tumor and abnormal protein burden rapidly and deeply to improve symptoms. In BNS, ibrutinib can be highly active and produce durable responses. In contrast, cBTKi are not recommended for treating AL amyloidosis. The panel emphasized that continuous improvement of treatment options for symptomatic, treatment-naïve WM patients critically depends on the participation of patients in clinical trials, whenever possible.Copyright © 2023. Published by Elsevier Inc.