Objective: This study aimed to summarize the clinical characteristics and prognosis of 108 patients with Waldenström macroglobulinemia (WM) in a single center and compare them with those of the Pivotal study with Bruton's tyrosine kinase inhibitor (BTKi) monotherapy. Methods: The clinical characteristics, international prognostic index score (IPSS) , first-line treatment, progression-free survival (PFS) , and overall survival (OS) of 108 patients with newly diagnosed WM from March 2008 to February 2021 were retrospectively evaluated. The MYD88 mutation was tested among 52 patients. Results: The median age of the 108 patients was 63 years (range, 38-78 years) with a male-to-female ratio of 3.5∶1. According to IPSS, we included 40% (n=43) high-risk, 33% (n=36) intermediate-risk, and 27% (n=29) low-risk patients. In this study, no significant difference was observed in age, gender, IPSS risk, serum immunoglobulin M (IgM) , and platelet counts compared to the baseline characteristics of 63 patients in the pivotal study. However, hemoglobin (86 g/L vs 105 g/L) , serum β(2)-MG (3.1 mg/L vs 3.9 mg/L) , bone marrow involvement (13% vs 60%) , and the proportion of adenopathy (41% vs 59%) were significantly lower than those in the Pivotal group. The proportion of patients with splenomegaly (27% vs 11%) was significantly higher than that of the Pivotal group. All the differences were statistically different (all P values <0.05) . The overall positive rate of MYD88 mutation was 77%. With a median follow-up of 36 (1-121) months, the median OS was 95 months, and the median PFS was 35 months. The 2-year OS rate (83% vs 96%) and 5-year OS rate (67% vs 87%) of patients with WM in our center were lower than those in the Pivotal group. The proportion of novel treatments based on BTKi, CD20 monoclonal antibody, and proteasome inhibitors in our center from 2008 to 2021 has gradually increased from 50% to 93%. The long-term OS of patients diagnosed in 2015-2021 was improved compared with that in 2008-2014 (P=0.048) . Conclusions: Novel drugs, including BTKi, continue to benefit patients with WM and improve their survival. It is worthwhile to further explore the positivity of MYD88 and CXCR4 mutations in the Chinese population and their sensitivity to BTKi.
目的： 总结上海交通大学医学院附属瑞金医院108例华氏巨球蛋白血症（WM）患者的临床特征和预后，并与应用BTK抑制剂（BTKi）单药的Pivotal研究比较。 方法： 回顾性分析2008年3月至2021年2月收治的症状性WM患者的临床特征、无进展生存（PFS）和总体生存（OS），其中52例患者进行MYD88突变检测。 结果： 108例患者中位年龄63（38~78）岁，男女比例3.5∶1。IPSS评分高危组43例（40%），中危组36例（33%），低危组29例（27%）。与Pivotal研究63例患者的基线特征比较，年龄、性别、IPSS危险度、血清IgM水平、PLT的差异无统计学意义，但HGB（86 g/L对105 g/L）、血清β(2)-微球蛋白（3.1 mg/L对3.9 mg/L）、骨髓受累（13%对60%）、淋巴结肿大比例（41%对59%）低于Pivotal研究患者，脾肿大患者比例（27%对11%）高于Pivotal研究，差异均有统计学意义（P值均<0.05）。MYD88突变整体检测阳性率77%。中位随访36（1~121）个月，中位OS时间为95个月，中位PFS时间为35个月。患者2年OS率（83%对96%）和5年OS率（67%对87%）低于Pivotal研究。2008-2021年，以BTKi、CD20单抗和蛋白酶体抑制剂治疗为主的患者比例从50%逐步提升至93%，2015-2021年诊断患者的长期OS较2008-2014年改善（P=0.048）。 结论： 包括BTKi在内的新药治疗使WM患者获益并改善其生存，中国WM患者MYD88和CXCR4突变检测阳性率及对BTKi的敏感性值得进一步探索。.
Keywords: Bruton's tyrosine kinase; Gene, MY88; Overall survival; Progression-free survival; Waldenström macroglobulinemia.