新型小分子药物在治疗慢性淋巴细胞白血病中的研究进展

Research Progress of Novel Small Molecule Drugs in the Treatment of Chronic Lymphocytic Leukemia——Review

慢性淋巴细胞白血病(chronic lymphocytic leukemia,CLL)是西方国家最常见的成人白血病,以CD5^+CD19^+CD23^+的B淋巴细胞在外周血、骨髓和淋巴结中的聚集为特征。在过去的20年里,CLL的治疗发生了一个戏剧性的变化,患者治疗后完全缓解率(complete responses,CR)由最初的<5%提高到了现在的40%-50%。这一进步归因于联合化学免疫疗法对慢性淋巴细胞白血病患者骨干的治疗,尤其近5年来一些新型药物的爆发式出现,给复发/难治患者和细胞遗传学异常患者的治疗提供了十分有效的方案。本文主要针对已被批准或已用于临床治疗CLL的新型小分子药物最新研究进展作一综述,讨论的主要药物包括布鲁顿酪氨酸激酶抑制剂(ibrutinib),P13K抑制剂(idelalisib),Syk抑制剂,BCL-2抑制剂等。

Chronic lymphocytic leukemia（CLL）,the most frequent adult leukemia in Western population,is characterized by accumulation of mature-looking CD5~＋/19~＋/23~＋ B cells in peripheral blood,bone marrow,and lymphatic organs.Over the last 20 years,there has been a dramatic change in therapy for CLL,the complete response rate increased from the initial 5%to the current 40%-50%,this remarkable improvement has been attributable to combination of chemoimmunotherapy agents that have contributed to the backbone of therapy for patients with CLL.Especially over the past 5 years,there has been an explosion of new active agents that provide a very effective solution for patients with recurrent/refractory disease as well as those who harbor poor cytogenetic abnormalities.This review focuses on some of the novel small molecule drugs that have either been approved or are at the forefront of clinical development in the treatment of patients with CLL,including tyrosine kinase inhibitior ibrutinib,PI3 K inhibitor idelalisib,Syk inhibitor,BCL-2 inhibitor and so on.