Kapoor Prashant, Dimopoulos Meletios A, Ansell Stephen M, Kastritis Efstathios, Advani Ranjana, Durot Eric, Morel Pierre, Kyriakou Charalampia, Hajek Roman, Drandi Daniela, Abeykoon Jithma P, Chow Signy, Cao Xinxin, Patterson Christopher J, Matous Jeffrey V, Buske Christian, Treon Steven P, Kersten Marie J
Mayo Clinic, Rochester MN.
Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece; Department of Medicine, Korea University, Seoul, South Korea.
Semin Hematol. 2025 Apr;62(2):90-105. doi: 10.1053/j.seminhematol.2025.04.001. Epub 2025 Apr 8.
The Consensus Panel 3 (CP3) of the 12th International Workshop on Waldenström macroglobulinemia (IWWM-12) has reviewed and incorporated current data to make recommendations for the management of patients with high-risk WM (HR-WM). Recognizing the considerable heterogeneity in survival outcomes and identifying a subgroup of patients with a very poor prognosis, the key recommendations from CP3 include: (1) Risk stratifying patients with smoldering WM (SWM) and active (symptomatic) WM at diagnosis (2) Using the degree of i) bone marrow lymphoplasmacytosis, ii) serum beta-2 microglobulin (β2M) elevation, iii) IgM increase, iv) serum albumin decrease and the presence of wild-type MYD88 status markers that adversely dictate the time-to-progression from smoldering to active WM to the define HR-SWM. (3) Among patients with active WM, the presenting parameters: advanced chronological age, low serum albumin, elevated serum lactate dehydrogenase, elevated β2M and the presence of TP53 alterations (TP53 mutation or deletion 17p) unfavorably impact the prognosis and should be utilized to risk-stratify patients into the HR category. (4) The panel encourages screening for genetic alterations at diagnosis, prior to initiating therapy and also with rapidly advancing disease or refractoriness to ongoing therapy, which might result from clonal evolution. Although limited data directing the selection and sequencing of therapies exist, a risk-adapted approach and clinical trial participation for patients with HR-WM are highly encouraged.
第12届华氏巨球蛋白血症国际研讨会（IWWM - 12）的共识小组3（CP3）回顾并纳入了当前数据，以对高危华氏巨球蛋白血症（HR - WM）患者的管理提出建议。认识到生存结果存在相当大的异质性，并确定了预后非常差的患者亚组，CP3的关键建议包括：（1）对诊断时的冒烟型WM（SWM）和活动性（有症状）WM患者进行风险分层；（2）使用以下程度来定义HR - SWM：i）骨髓淋巴浆细胞增多症、ii）血清β2微球蛋白（β2M）升高、iii）IgM增加、iv）血清白蛋白降低以及野生型MYD88状态标志物的存在，这些因素会对从冒烟型到活动性WM的进展时间产生不利影响；（3）在活动性WM患者中，以下呈现参数：高龄、低血清白蛋白、血清乳酸脱氢酶升高、β2M升高以及TP53改变（TP53突变或17p缺失）会对预后产生不利影响，应用于将患者风险分层为HR类别；（4）该小组鼓励在诊断时、开始治疗前以及疾病快速进展或对正在进行的治疗难治时进行基因改变筛查，这可能是由于克隆进化导致的。尽管指导治疗选择和测序的数据有限，但强烈鼓励HR - WM患者采用风险适应性方法并参与临床试验。
