Morabito Fortunato, Recchia Anna Grazia, Vigna Ernesto, De Stefano Laura, Bossio Sabrina, Morabito Lucio, Pellicanò Mariavaleria, Palummo Angela, Storino Francesca, Caruso Nadia, Gentile Massimo
Azienda Ospedaliera di Cosenza, Dipartimento Oncoematologico, Unità Operativa Complessa di Ematologia , Viale della Repubblica, Cosenza 87100 , Italy +39 0984 681329 ; +39 0984 681866 ;
Expert Opin Investig Drugs. 2015 Jun;24(6):795-807. doi: 10.1517/13543784.2015.1021920. Epub 2015 Mar 1.
The combination schedule of fludarabine, cyclophosphamide and rituximab is the gold standard of therapy for younger, physically fit chronic lymphocytic leukemia (CLL) patients; it allows achieving high and durable complete response rates. Although treatment outcome has considerably improved with chemo-immunotherapy, most patients eventually relapse and CLL is still incurable. Thus, newer and more rationally developed drugs are needed to improve CLL therapy, particularly in cases of relapsed/refractory disease.
The authors review preclinical and clinical data regarding newer CLL agents, currently undergoing examination, such as: signal transduction and cyclin-dependent kinase inhibitors, immunomodulatory agents, B-cell lymphoma 2 inhibitors, next generation mAbs, heat shock protein 90 and histone deacetylase inhibitors, and chimeric antigen receptor T-cell therapy.
Newer compounds with different mechanisms of action, such as B-cell receptor signal transduction inhibitors, lenalidomide, next generation mAbs and several pro-apoptotic molecules, have shown efficacy in relapsed or refractory CLL patients. Several studies are under way to investigate the efficacy of combinations of these novel drugs. Hopefully, the combined use of these molecules in risk-adapted treatment strategies will change the therapeutic approach in the near future and will pave the way for a long-term control of CLL.
氟达拉滨、环磷酰胺和利妥昔单抗联合方案是年轻、身体状况良好的慢性淋巴细胞白血病（CLL）患者治疗的金标准；它能实现高且持久的完全缓解率。尽管化疗免疫疗法使治疗结果有了显著改善，但大多数患者最终仍会复发，CLL仍然无法治愈。因此，需要更新且更合理研发的药物来改善CLL治疗，尤其是在复发/难治性疾病的情况下。
作者回顾了有关目前正在研究的新型CLL药物的临床前和临床数据，例如：信号转导和细胞周期蛋白依赖性激酶抑制剂、免疫调节剂、B细胞淋巴瘤2抑制剂、新一代单克隆抗体、热休克蛋白90和组蛋白去乙酰化酶抑制剂，以及嵌合抗原受体T细胞疗法。
具有不同作用机制的新型化合物，如B细胞受体信号转导抑制剂、来那度胺、新一代单克隆抗体和几种促凋亡分子，已在复发或难治性CLL患者中显示出疗效。正在进行多项研究以调查这些新型药物联合使用的疗效。有望在不久的将来，这些分子在风险适应性治疗策略中的联合使用将改变治疗方法，并为CLL的长期控制铺平道路。
