Division of Hematology Oncology, Department of Medicine, Medical College of Georgia, Augusta, GA, USA.
Leuk Lymphoma. 2010 Jan;51(1):27-38. doi: 10.3109/10428190903350405.
The use of nucleoside analog-based chemo-immunotherapeutic regimens over the last decade has significantly improved outcomes in patients with chronic lymphocytic leukemia (CLL). Nonetheless, virtually all patients with CLL relapse from chemoimmmunotherapy and current available therapies are not curative. Identifying therapies that effectively eliminate CLL cells and lack immunesuppression represent an exciting new therapeutic approach. IMiDs are a class of immunomodulating drugs that increase T-cell and NK-cell directed killing of tumor cells. The first generation molecule is thalidomide followed by a second generation molecule lenalidomide that lacks neurotoxicity and is being explored more extensively in clinical trials. Lenalidomide has been shown to benefit patients with multiple myeloma, myelodysplastic syndromes, and lymphoma. Initial reports in patients with relapsed and refractory CLL have shown promising responses. In a subset of patients with CLL complete responses have been noted. Subsequent studies, however, have suggested that this class of drug can also have serious and potentially life-threatening side effects including myelosuppression, tumor flare reaction and in a small subset of patients tumor lysis syndrome. Tumor flare with both thalidomide and lenalidomide appear to be disease specific to CLL and may reflect clinical manifestation of CLL tumor cell activation. As a consequence of these disease specific effects, the optimal safe dose of lenalidomide in CLL remains to be determined but appears to be lower than that tolerated in other B-cell malignancies. To date, biomarkers for response remain poorly defined and the relationship of clinical benefit to tumor flare is uncertain. This review examines the existing literature on the use of IMiDs in patients with CLL and provides suggestions for future research in this area.
过去十年中，基于核苷类似物的化疗-免疫治疗方案的使用显著改善了慢性淋巴细胞白血病（CLL）患者的预后。尽管如此，几乎所有 CLL 患者都会从化疗免疫治疗中复发，而目前可用的治疗方法并非治愈性的。寻找能够有效消除 CLL 细胞且缺乏免疫抑制作用的疗法代表了一种令人兴奋的新治疗方法。IMiD 是一类免疫调节药物，可增加 T 细胞和 NK 细胞对肿瘤细胞的定向杀伤。第一代分子是沙利度胺，其次是第二代分子来那度胺，它没有神经毒性，并且在临床试验中得到了更广泛的探索。来那度胺已被证明对多发性骨髓瘤、骨髓增生异常综合征和淋巴瘤患者有益。在复发和难治性 CLL 患者中的初步报告显示出有希望的反应。在一小部分 CLL 患者中观察到完全缓解。然而，随后的研究表明，这类药物也可能具有严重且潜在威胁生命的副作用，包括骨髓抑制、肿瘤爆发反应和在一小部分患者中肿瘤溶解综合征。沙利度胺和来那度胺都出现的肿瘤爆发似乎是 CLL 特有的疾病，可能反映了 CLL 肿瘤细胞激活的临床表现。由于这些疾病特异性效应，来那度胺在 CLL 中的最佳安全剂量仍有待确定，但似乎低于其他 B 细胞恶性肿瘤耐受的剂量。迄今为止，反应的生物标志物仍然定义不明确，临床获益与肿瘤爆发之间的关系尚不确定。这篇综述检查了关于来那度胺在 CLL 患者中的使用的现有文献，并为该领域的未来研究提供了建议。
