肿瘤细胞治疗研究
英文原题：SOHO State-of-the-Art Updates and Next Questions: Current Approach to Waldenström Macroglobulinemia.
华氏巨球蛋白血症（WM）或免疫球蛋白M（IgM）淋巴浆细胞淋巴瘤是一种异质性的临床病理实体，具有一些显著特征，包括循环单克隆IgM、淋巴浆细胞骨髓浸润，以及在超过90%的患者中存在复发性克隆性突变MYD88 L265。
华氏巨球蛋白血症（WM）或免疫球蛋白M（IgM）淋巴浆细胞淋巴瘤是一种异质性临床病理实体，具有一些特征性表现，包括循环单克隆IgM、淋巴浆细胞性骨髓浸润，以及超过90%的患者存在复发性克隆性突变MYD88 L265。临床表现高度可变。有症状且具备开始治疗指征的患者，初始管理可采用固定疗程的化学免疫治疗（例如苯达莫司汀-利妥昔单抗）或共价Bruton酪氨酸激酶（BTK）抑制剂（例如泽布替尼），后者持续给药直至疾病进展或出现不可耐受毒性，尽管这两种高度不同的方法尚未在随机试验中直接比较。MYD88 L265P、CXCR4和TP53突变状态可能影响治疗决策。WM的管理选择正在扩大，因为近期多项试验显示BCL-2抑制剂、非共价BTK抑制剂和BTK降解剂在既往暴露于或难治于共价BTK抑制剂和/或化学免疫治疗的患者中具有有希望的疗效。涉及CAR-T细胞和双特异性抗体的新方法的初步数据正在不断产生，迄今为止的报告令人鼓舞。
Waldenstr m macroglobulinemia (WM) or Immunoglobulin M (IgM) lymphoplasmacytic lymphoma is a heterogeneous clinicopathologic entity with distinguishing features that include circulating monoclonal IgM, lymphoplasmacytic marrow infiltrate, and in > 90% of patients, a recurrent clonal mutation, MYD88 L265 . The clinical manifestations are highly variable. Symptomatic patients with indication(s) to start therapy are initially managed with either fixed-duration chemoimmunotherapy (for example, bendamustine-rituximab) or a covalent Bruton tyrosine kinase (BTK) inhibitor (for example, zanubrutinib) given until progression or intolerable toxicity, although these 2 highly different approaches have not been directly compared in randomized trials. MYD88 L265P , CXCR4, and TP53 mutational status may potentially impact treatment decision-making. Options for managing WM are expanding as several recent trials demonstrate the promising efficacy of BCL-2 inhibitors, noncovalent BTK inhibitors and BTK degraders in patients that are previously exposed, or refractory, to a covalent BTK inhibitor and/or chemoimmunotherapy. Preliminary data with novel approaches involving CAR-T cell and bispecific antibodies are continuing to be generated, and the reports, thus far, are encouraging.
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