Department of Experimental Hematology, Medical University of Lodz , Lodz, Poland.
Expert Opin Pharmacother. 2020 Oct;21(15):1915-1926. doi: 10.1080/14656566.2020.1791083. Epub 2020 Jul 20.
The outcome of patients with lymphoid malignancies has markedly improved in recent years due to the implementation of new therapeutic options. Chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphomas (NHL) are characterized by the activation of the phosphatidylinositol 3-kinase (PI3 K) pathway B-cell receptor signaling. The PI3 K delta (PI3 Kδ) p110δ isoform inhibitor, idelalisib, showed high anti-tumor activity in this group of tumors. It was the first agent from a new class of isoform-specific inhibitors to receive regulatory approvals for the treatment of refractory/relapsed CLL, as well as small lymphocytic lymphoma and follicular lymphoma.
In this paper, the authors provide a comprehensive overview of the activity and safety profile of idelalisib and other, newly developed PI3 K inhibitors in patients with indolent B-cell malignancies.
Idelalisib is a very potent anti-lymphoma agent in CLL and other NHL. However, there are some limitations of its broad clinical use according to some important side effects observed during treatment. Consequently, the development of new PI3 K inhibitors, which will be highly active and possess better safety profiles are warranted.
近年来,由于新的治疗选择的实施,淋巴恶性肿瘤患者的预后有了显著改善。慢性淋巴细胞白血病(CLL)和惰性 B 细胞非霍奇金淋巴瘤(NHL)的特征是磷酸肌醇 3-激酶(PI3K)途径和 B 细胞受体信号的激活。PI3Kδ(PI3Kδ)p110δ 同工型抑制剂idelalisib 在这组肿瘤中表现出很高的抗肿瘤活性。它是第一个获得监管批准用于治疗难治/复发 CLL、小淋巴细胞淋巴瘤和滤泡性淋巴瘤的新型同工型特异性抑制剂类药物。
本文作者全面概述了 idelalisib 及其他新开发的 PI3K 抑制剂在惰性 B 细胞恶性肿瘤患者中的疗效和安全性概况。
idelalisib 是 CLL 和其他 NHL 中非常有效的抗淋巴瘤药物。然而,根据治疗期间观察到的一些重要副作用,其广泛临床应用存在一些局限性。因此,有必要开发新的 PI3K 抑制剂,这些抑制剂将具有更高的活性和更好的安全性。