Itchaki Gilad, Brown Jennifer R
a Department of Medical Oncology , Dana Farber Cancer Institute , Boston , MA , USA.
Expert Opin Investig Drugs. 2017 May;26(5):633-650. doi: 10.1080/13543784.2017.1313230. Epub 2017 Apr 17.
Lenalidomide is an immunomodulatory drug (IMiD) with a unique mode of action (MOA) that may vary across disease-type. It is currently approved in multiple myeloma (MM), myelodysplastic syndrome (MDS) and mantle cell lymphoma (MCL), yet is also clinically active in a host of lymphoproliferative diseases, including chronic lymphocytic leukemia (CLL). Due to its protean effects on the immune system, lenalidomide may be particularly appealing in CLL, which is distinct in its ability to evade immune recognition and cause immunosuppression. Areas covered: This review recaps the biological mechanisms of lenalidomide specific for CLL, and summarizes the clinical data in previously untreated and relapsed/refractory (R/R) CLL patients, with emphasis on toxicity. Moreover, lenalidomide treatment is put into the context of the highly effective targeted agents that are drastically changing the therapeutic approach in CLL. Expert opinion: Lenalidomide is a potent drug in CLL, both in first line and relapse. However, in comparison to other newly available agents, lenalidomide has slow onset of efficacy and notable toxicity profile that limits both its single agent use and combinations with chemotherapy. Future trials will hopefully direct our ability to harness lenalidomide MOA to best incorporate it in the rapidly evolving landscape of CLL treatment.
来那度胺是一种免疫调节药物(IMiD),具有独特的作用模式(MOA),可能因疾病类型而异。它目前已被批准用于治疗多发性骨髓瘤(MM)、骨髓增生异常综合征(MDS)和套细胞淋巴瘤(MCL),但在包括慢性淋巴细胞白血病(CLL)在内的许多淋巴增殖性疾病中也具有临床活性。由于其对免疫系统的多种作用,来那度胺在CLL中可能特别有吸引力,CLL在逃避免疫识别和导致免疫抑制方面具有独特能力。涵盖领域:本综述回顾了来那度胺对CLL具有特异性的生物学机制,并总结了既往未治疗和复发/难治性(R/R)CLL患者的临床数据,重点关注毒性。此外,将来那度胺治疗置于正在彻底改变CLL治疗方法的高效靶向药物背景下进行讨论。专家意见:来那度胺在CLL的一线治疗和复发治疗中都是一种有效的药物。然而,与其他新出现的药物相比,来那度胺起效缓慢,毒性显著,这限制了其单药使用以及与化疗联合使用。未来的试验有望指导我们利用来那度胺的作用模式,以便在CLL治疗快速发展的格局中最佳地纳入该药物。