第11届Waldenstrom巨球蛋白血症国际研讨会(IWWM-11)的共识小组1(CP1)的任务是更新对症治疗指南,治疗初治WM患者。专家组重申,对于没有IgM严重升高或造血功能受损的无症状患者,观察等待仍然是黄金标准。对于一线治疗,化学免疫疗法(CIT)方案,如地塞米松,环磷酰胺,利妥昔单抗(DRC),或者苯达莫司汀,利妥昔单抗(Benda-R)继续在管理WM中发挥核心作用,因为它们是有效的,固定期限,一般耐受性良好,和负担得起的。共价BTK抑制剂(cBTKi)提供了一种连续的,对于WM患者的主要治疗,通常耐受性良好的替代方案,特别是那些不适合CIT.在IWWM-11更新的III期随机试验中,第二代cBTKi,扎努布替尼,毒性比ibrutinib小,并引起更深的缓解,因此将扎努鲁替尼归类为WM的合适治疗选择。虽然总体调查结果的前瞻性,在IWWM-11上更新的随机试验未显示在达到Benda-R诱导的主要反应后,固定时间利妥昔单抗维持治疗优于观察,一项子集分析显示,65岁以上患者和IPPSWM评分较高的患者获益.只要有可能,MYD88和CXCR4的突变状态应在治疗开始前确定,因为这两个基因的改变预测了对cBTKi活性的敏感性。WM相关冷球蛋白的治疗方法,冷凝集素,AL淀粉样变性,Bing-Neel综合征(BNS),周围神经病变,高粘血症遵循快速、深入地减少肿瘤和异常蛋白负荷以改善症状的共同原则。在BNS,伊布替尼可以是高度活跃的,并产生持久的反应。相比之下,cBTKi不推荐用于治疗AL淀粉样变性。小组强调,持续改进对症治疗方案,初治WM患者的治疗关键取决于患者在临床试验中的参与,只要有可能。
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.