Department of Pharmacy, M. D. Anderson Cancer Center , Houston, TX , USA.
Leuk Lymphoma. 2013 Dec;54(12):2592-600. doi: 10.3109/10428194.2013.789509. Epub 2013 Jun 21.
Conventional cytotoxic chemotherapy for adult acute lymphoblastic leukemia (ALL) is not adequate to cure most patients of the disease. Complete remission is achieved in the majority of patients, but responses are often not durable. Allogeneic stem cell transplant is used for patients with high risk features, including those who are positive for minimal residual disease after induction and consolidation therapy. Nevertheless, transplant is a toxic intervention, and does not guarantee long-term disease-free survival. Monoclonal antibodies target surface antigens present on leukemic blasts, with the aim of minimizing off-target toxicity. Rituximab, an antibody directed against CD20, prolongs the survival of younger adults with ALL when added to chemotherapy in the frontline setting. Novel agents, such as the cytotoxin-antibody conjugate inotuzumab, and the bispecific T-cell engaging compound blinatumomab, have exhibited marked antileukemic activity in the relapsed setting. As these agents continue in clinical development, it will be important to eventually incorporate them in the frontline treatment approach. We review current strategies for treating adult ALL, with a focus on novel and targeted therapies that are under development.
传统的成人急性淋巴细胞白血病(ALL)细胞毒化疗不足以治愈大多数患者。大多数患者可获得完全缓解,但缓解往往不能持久。异体干细胞移植用于具有高危特征的患者,包括诱导和巩固治疗后微小残留病阳性的患者。然而,移植是一种有毒的干预措施,并不能保证长期无病生存。单克隆抗体针对白血病细胞表面抗原,旨在最大限度地减少非靶向毒性。利妥昔单抗是一种针对 CD20 的抗体,当与化疗联合用于一线治疗时,可延长年轻成人 ALL 的生存时间。新型药物,如细胞毒素-抗体偶联物 inotuzumab 和双特异性 T 细胞结合化合物blinatumomab,在复发时表现出显著的抗白血病活性。随着这些药物在临床开发中的不断推进,最终将它们纳入一线治疗方法非常重要。我们回顾了目前治疗成人 ALL 的策略,重点介绍了正在开发的新型和靶向治疗药物。