Maffei Rossana, Colaci Elisabetta, Fiorcari Stefania, Martinelli Silvia, Potenza Leonardo, Luppi Mario, Marasca Roberto
Hematology Unit, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Hematology Unit, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Crit Rev Oncol Hematol. 2016 Jan;97:291-302. doi: 10.1016/j.critrevonc.2015.09.003. Epub 2015 Sep 30.
Lenalidomide is an immunomodulatory agent (IMiD) clinically active in chronic lymphocytic leukemia (CLL), both in heavily pre-treated patients and upfront. Lenalidomide has a unique mechanism of action in CLL. Its efficacy relies on a multifactorial mode-of-action (MOA), comprising a plethora of immunomodulatory actions, the disruption of mutualistic interactions inside CLL microenvironment and direct effects against leukemic cells. In the last few years, a number of new and highly effective drugs appeared in the scenario of CLL therapeutic options, i.e. tyrosine kinase inhibitors (TKIs), showing a good safety profile and impressive clinical response, also in high-risk patients. In this review, we describe the data from clinical studies about lenalidomide efficacy in CLL and we critically dissect the different mechanisms of action of this drug. We point the attention on open issues, including drug dosage and administration schedule, prediction of clinical response to lenalidomide, and combination therapeutic strategies. This overview would be useful to envision a possible role of lenalidomide in the treatment flow-chart of CLL, exploiting its peculiar MOA and also exploring the possible synergetic effect with new drugs.
来那度胺是一种免疫调节剂（IMiD），在慢性淋巴细胞白血病（CLL）中具有临床活性，无论是在经过大量预处理的患者还是初治患者中。来那度胺在CLL中具有独特的作用机制。其疗效依赖于多因素作用模式（MOA），包括大量免疫调节作用、破坏CLL微环境内的共生相互作用以及对白血病细胞的直接作用。在过去几年中，一些新型高效药物出现在CLL治疗选择的场景中，即酪氨酸激酶抑制剂（TKIs），在高危患者中也显示出良好的安全性和令人印象深刻的临床反应。在本综述中，我们描述了关于来那度胺在CLL中疗效的临床研究数据，并批判性地剖析了该药物的不同作用机制。我们将注意力集中在未解决的问题上，包括药物剂量和给药方案、对来那度胺临床反应的预测以及联合治疗策略。这一概述将有助于设想来那度胺在CLL治疗流程图中的可能作用，利用其独特的MOA，并探索与新药可能的协同效应。
