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Target Oncol. 2015 Mar;10(1):141-51. doi: 10.1007/s11523-015-0359-8. Epub 2015 Feb 1.
Idelalisib (Zydelig®) is a first-in-class, orally administered, phosphatidylinositol 3-kinase-δ inhibitor that was recently approved for the treatment of relapsed chronic lymphocytic leukaemia (CLL), relapsed follicular B-cell non-Hodgkin's lymphoma (NHL) and relapsed small lymphocytic lymphoma (SLL) in the USA and for the treatment of CLL and refractory follicular lymphoma in the EU. In a pivotal phase III trial in patients with relapsed CLL who were not able to receive cytotoxic agents, recipients of idelalisib plus rituximab had significantly improved progression-free survival, overall survival, overall response and lymph node response, compared with recipients of placebo plus rituximab. In a pivotal phase II trial, idelalisib monotherapy was effective in patients with relapsed indolent NHL who were refractory to rituximab and an alkylating agent, including in the subgroups of patients with follicular lymphoma or SLL. Oral idelalisib had a generally manageable adverse event profile, although episodes of serious/fatal diarrhoea or colitis, hepatotoxicity, pneumonitis and intestinal perforation were reported. In conclusion, idelalisib represents an important advance in the treatment of relapsed CLL and relapsed indolent NHL.
依鲁替尼(泽达利®)是一种首创的、口服给药的、磷酸肌醇 3-激酶-δ 抑制剂,最近在美国被批准用于治疗复发的慢性淋巴细胞白血病(CLL)、复发滤泡 B 细胞非霍奇金淋巴瘤(NHL)和复发小淋巴细胞淋巴瘤(SLL),以及在欧盟用于治疗 CLL 和难治性滤泡淋巴瘤。在一项复发 CLL 患者的关键 III 期试验中,不能接受细胞毒性药物治疗的患者接受依鲁替尼联合利妥昔单抗治疗,与接受安慰剂联合利妥昔单抗治疗的患者相比,无进展生存期、总生存期、总缓解率和淋巴结缓解率显著提高。在一项关键的 II 期试验中,依鲁替尼单药治疗对复发的惰性 NHL 患者有效,这些患者对利妥昔单抗和烷化剂耐药,包括滤泡淋巴瘤或 SLL 亚组患者。口服依鲁替尼的不良反应谱一般可管理,但有严重/致命腹泻或结肠炎、肝毒性、肺炎和肠穿孔的报告。总之,依鲁替尼是复发 CLL 和复发惰性 NHL 治疗的重要进展。