Advances in the molecular biology of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and development of molecularly targeted therapies have resulted in treatment innovations. Therapeutic approaches for previously untreated CLL/SLL patients are changing from chemoimmunotherapy (CIT) to molecularly targeted drugs. The aim of therapy for CLL patients has been to control the disease; however, FCR (fludarabine, cyclophosphamide, rituximab) has improved outcomes and reduced the high incidence of undetectable minimum/measurable residual disease (MRD) in previously untreated CLL patients with no 17p deletion/TP53 disruption and mutated immunoglobulin heavy chain gene (IGHV). Patients achieving undetectable MRD in the bone marrow are expected to be cured. BTK inhibitors and BCL-2 inhibitors are effective for CLL/SLL patients. However, atrial fibrillation and bleeding are associated with the BTK inhibitor, ibrutinib, while tumor lysis syndrome is an adverse event (AE) of the BCL-2 inhibitor, venetoclax. Although these novel targeted drugs are very useful, they are also expensive. Emergence of resistant clones of CLL cells must also be addressed. Therefore, treatments of indefinite duration until progression have been replaced by fixed-duration treatments. This review introduces advances in the treatment of previously untreated CLL/SLL patients in Europe and the United States.

中文翻译：

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日本慢性淋巴细胞白血病管理的演变：MRD 阴性是否应该成为目标？

慢性淋巴细胞性白血病/小淋巴细胞性淋巴瘤（CLL/SLL）分子生物学的进步和分子靶向治疗的发展带来了治疗创新。以前未经治疗的 CLL/SLL 患者的治疗方法正在从化学免疫疗法 (CIT) 转变为分子靶向药物。CLL 患者的治疗目标一直是控制疾病；然而，FCR（氟达拉滨、环磷酰胺、利妥昔单抗）改善了预后，并降低了既往未接受治疗且没有 17p 缺失/TP53 破坏和免疫球蛋白重链基因 (IGHV) 突变的 CLL 患者无法检测到的最小/可测量残留病 (MRD) 的高发生率。在骨髓中达到无法检测到的 MRD 的患者有望治愈。BTK 抑制剂和 BCL-2 抑制剂对 CLL/SLL 患者有效。然而，心房颤动和出血与 BTK 抑制剂依鲁替尼有关，而肿瘤溶解综合征是 BCL-2 抑制剂 venetoclax 的不良事件 (AE)。尽管这些新型靶向药物非常有用，但它们也很昂贵。还必须解决 CLL 细胞抗性克隆的出现。因此，直到进展的无限期治疗已被固定持续时间的治疗所取代。这篇综述介绍了欧洲和美国在治疗以前未经治疗的 CLL/SLL 患者方面取得的进展。还必须解决 CLL 细胞抗性克隆的出现。因此，直到进展的无限期治疗已被固定持续时间的治疗所取代。这篇综述介绍了欧洲和美国在治疗以前未经治疗的 CLL/SLL 患者方面取得的进展。还必须解决 CLL 细胞抗性克隆的出现。因此，直到进展的无限期治疗已被固定持续时间的治疗所取代。这篇综述介绍了欧洲和美国在治疗以前未经治疗的 CLL/SLL 患者方面取得的进展。