Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management
Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management
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DOI：
10.1002/ajh.25487
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发表时间：
2019-06-01
影响因子：
12.8
通讯作者：
Wang, Michael
中科院分区：
文献类型：
--
作者：
Jain, Preetesh;Wang, Michael
在过去的几年里，我们对套细胞淋巴瘤（MCL）的病理生物学、诊断和治疗选择的理解取得了前所未有的进展。通过与免疫球蛋白重链可变区的突变状态、甲基化状态和SOX-11表达的相关性，进一步描述了MCL-indolent vs aggressive临床过程中的异质性。细胞周期蛋白-D1阴性MCL，原位MCL瘤形成，以及染色体核型对预后的影响进行了区分。除了Ki-67%和形态学模式（经典型与胚状/多形性）外，增殖基因特征有助于进一步完善分类。关注布鲁顿酪氨酸激酶（BTK）抑制剂（伊替尼、acalabrutinib）和/或Bcl 2拮抗剂（维奈托克）的突变动力学和克隆进化的研究进一步阐明了TP 53、BIRC 3、CDKN 2A、MAP 3 K14、N 0 TCH 2、NSD 2和SMARCA 4基因中体细胞突变的预后影响。在治疗方面，对化学免疫治疗研究的长期随访表明，一些患者的病情可持续缓解;然而，长期毒性，特别是继发性癌症，是化疗的一个严重问题。MCL的治疗选择在不断发展，非化疗药物（伊曲替尼、acalabrutinib和venetoclax）的疗效显著。嵌合抗原受体治疗和非化疗药物的组合正在积极研究中，我们的重点正在转向使MCL的治疗化疗免费。尽管如此，MCL仍然无法治愈。MCL的以下方面继续构成挑战：疾病转化，肿瘤微环境的作用，正电子发射断层扫描-计算机断层扫描成像的结合，预后中的最小残留疾病，循环肿瘤DNA克隆进化检测，预测对BTK抑制剂的耐药性，以及对BTK/Bcl 2抑制剂进展的患者的最佳管理。下一代临床试验应该包括非化疗药物，并根据个体患者的基因组特征进行个性化治疗。本文综述了近年来微胶囊发光领域的研究进展。
Unprecedented advances in our understanding of the pathobiology, prognostication, and therapeutic options in mantle cell lymphoma (MCL) have taken place in the last few years. Heterogeneity in the clinical course of MCL-indolent vs aggressive-is further delineated by a correlation with the mutational status of the variable region of immunoglobulin heavy chain, methylation status, and SOX-11 expression. Cyclin-D1 negative MCL, in situ MCL neoplasia, and impact of the karyotype on prognosis are distinguished. Apart from Ki-67% and morphology pattern (classic vs blastoid/pleomorphic), the proliferation gene signature has helped to further refine prognostication. Studies focusing on mutational dynamics and clonal evolution on Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib) and/or Bcl2 antagonists (venetoclax) have further clarified the prognostic impact of somatic mutations in TP53, BIRC3, CDKN2A, MAP3K14, NOTCH2, NSD2, and SMARCA4 genes. In therapy, long-term follow-up on chemo-immunotherapy studies has demonstrated durable remissions in some patients; however, long-term toxicities, especially from second cancers, are a serious concern with chemotherapy. The therapeutic options in MCL are constantly evolving, with dramatic responses from nonchemotherapeutic agents (ibrutinib, acalabrutinib, and venetoclax). Chimeric antigen receptor therapy and combinations of nonchemotherapeutic agents are actively being studied and our focus is shifting toward making the treatment of MCL chemotherapy-free. Still, MCL remains incurable. The following aspects of MCL continue to pose a challenge: disease transformation, role of the cytokine-microenvironmental milieu, incorporation of positron emission tomography-computerized tomography imaging, minimal residual disease in the prognosis, circulating tumor DNA testing for clonal evolution, predicting resistance to BTK inhibitors, and optimal management of patients who progress on BTK/Bcl2 inhibitors. Next-generation clinical trials should incorporate nonchemotherapeutic agents and personalize the treatment based upon the genomic profile of individual patient. Recent advances in the field of MCL are reviewed.