Hospices Civils de Lyon, Service d'Hématologie, Pierre Bénite Cedex, France. Université Claude Bernard, Faculté de Médecine Lyon-Sud Charles Mérieux, Université de Lyon, Pierre Bénite Cedex, France.
Clin Cancer Res. 2014 Oct 15;20(20):5226-39. doi: 10.1158/1078-0432.CCR-14-0437.
Indolent B-cell lymphomas are heterogeneous, comprising three grades of follicular lymphoma, small lymphocytic lymphoma, Waldenstöm macroglobulinemia, marginal zone lymphoma, and most recently, possibly low proliferative mantle cell lymphoma. These lymphomas are characterized by a high responsiveness to chemotherapy or immunochemotherapy; however, in most cases, conventional therapy might not offer a cure. Furthermore, the patient's age at diagnosis, at time to first or subsequent relapses, as well as potential comorbidities often preclude the use of chemotherapy. Recent progress has been made in our understanding of dysregulated pathways and immunologic antitumor responses in indolent lymphoma. Major therapeutic advances have been achieved in the development of nonchemotherapeutic agents, making "chemo-free" treatment a near-future reality. In this article, we highlight these promising approaches, such as the combination of anti-CD20 antibodies with immunomodulatory drugs, with mAbs directed against other surface antigens such as CD22, with immunomodulatory antibodies such as PD-1, or with inhibitors of key steps in the B-cell receptor pathway signaling. However, the cost of such therapies and potential, albeit manageable, toxicity should be considered. Phase III trials will confirm the benefit of these new treatment strategies that do not require a chemotherapeutic drug and help us identify their exact place in the therapeutic armamentarium for indolent lymphoma. Here we focus on follicular lymphoma, which is the most frequent subtype of indolent lymphoma and for which an increasing body of evidence has emerged that supports the dawn of a new era of chemotherapy-free treatment. See all articles in this CCR Focus section, "Paradigm Shifts in Lymphoma."
惰性 B 细胞淋巴瘤具有异质性，包括滤泡性淋巴瘤、小淋巴细胞淋巴瘤、华氏巨球蛋白血症、边缘区淋巴瘤，以及最近可能的低增殖性套细胞淋巴瘤等三种分级。这些淋巴瘤对化疗或免疫化疗具有高度反应性；然而，在大多数情况下，常规疗法可能无法治愈。此外，患者的诊断年龄、首次或后续复发时间以及潜在的合并症常常排除了化疗的使用。最近，我们对惰性淋巴瘤中失调的途径和免疫抗肿瘤反应有了更多的了解。在开发非化疗药物方面取得了重大治疗进展，使得“无化疗”治疗成为不久的将来的现实。在本文中，我们强调了这些有前途的方法，例如将抗 CD20 抗体与免疫调节剂联合使用，与针对其他表面抗原（如 CD22）的 mAbs 联合使用，与免疫调节剂抗体（如 PD-1）联合使用，或与 B 细胞受体途径信号传导的关键步骤抑制剂联合使用。然而，应该考虑到这些疗法的成本和潜在的、尽管可以管理的毒性。III 期试验将证实这些不需要化疗药物的新治疗策略的益处，并帮助我们确定它们在惰性淋巴瘤治疗武器库中的确切位置。在这里，我们重点关注滤泡性淋巴瘤，这是最常见的惰性淋巴瘤亚型，越来越多的证据表明，它开创了一个无化疗治疗的新时代。参见 CCR 焦点部分的所有文章，“淋巴瘤的范式转变”。
