In the last few years, several agents targeting molecules that sustain the survival and the proliferation of chronic lymphocytic leukemia (CLL) cells have become clinically available. Most of these drugs target surface proteins, such as CD19 or CD20, via monoclonal or bispecific monoclonal antibodies (BsAbs), CAR T cells, intracellular proteins like BTK by using covalent or non-covalent inhibitors or BCL2 with first or second generation BH3-mimetics. Since the management of CLL is evolving quickly, in this review we highlighted the most important innovative treatments including novel double and triple combination therapies, CAR T cells and BsAbs for CLL. Recently, a large number of studies on novel combinations and newer strategic options for CLL therapy have been published or presented at international conferences, which were summarized and linked together. Although the management of treatment with a single continuous agent is easier, the emergence of protein mutations, long-term toxicities and costs are important concerns that favor the use of a fixed duration therapy. In the future, a measurable residual disease (MRD)-guided treatment cessation and MRD-based re-initiation of targeted therapy seems to be a more feasible approach, allowing identification of the patients who might benefit from continuous therapy or who might need a consolidation with BsAbs or CAR T cells to clear the neoplastic clone.
近年来，多种靶向慢性淋巴细胞白血病（CLL）细胞生存与增殖关键分子的药物已进入临床应用。这些药物主要通过以下机制发挥作用：针对CD19或CD20等表面蛋白的单克隆抗体或双特异性单克隆抗体（BsAbs）、CAR T细胞疗法；通过共价或非共价抑制剂靶向BTK等细胞内蛋白；以及采用第一代或第二代BH3模拟物抑制BCL2蛋白。随着CLL治疗策略的快速演进，本综述重点探讨了包括新型双重及三重联合疗法、CAR T细胞和BsAbs在内的创新治疗方案。近期，大量关于CLL新型联合疗法及创新治疗策略的研究已在国际会议发表或展示，本文对这些进展进行了系统性梳理与整合。尽管单药持续治疗方案更易于管理，但蛋白突变的发生、长期毒性及治疗成本等问题促使固定疗程治疗受到更多关注。未来，以可测量残留病灶（MRD）为指导的治疗暂停策略及基于MRD检测重启靶向治疗的方案可能更具可行性。该策略有助于识别两类患者群体：一类可能从持续治疗中获益，另一类则可能需要通过BsAbs或CAR T细胞进行巩固治疗以清除肿瘤克隆。
肿瘤(癌症)患者之家