A phase 2 study of idelalisib plus rituximab in treatment-naive older patients with chronic lymphocytic leukemia
A phase 2 study of idelalisib plus rituximab in treatment-naive older patients with chronic lymphocytic leukemia
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DOI：
10.1182/blood-2015-03-630947
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发表时间：
2015-12-17
期刊：
影响因子：
20.3
通讯作者：
Coutre, Steven E.
中科院分区：
文献类型：
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作者：
O'Brien, Susan M.;Lamanna, Nicole;Coutre, Steven E.
Idelalisib是一类PI 3 K δ口服抑制剂，在复发性/难治性慢性淋巴细胞白血病（CLL）患者中显示出显著活性。为了评估艾代拉里斯作为初始治疗的效果，64例初治的CLL或小淋巴细胞白血病老年患者（中位年龄71岁;范围65-90岁）接受利妥昔单抗375 mg/m2每周一次x8和艾代拉里斯150 mg每日两次连续治疗48周。完成48周无进展的患者可以在扩展研究中继续接受idelalisib。中位治疗时间为22.4个月（范围：0.8-45.81）。总缓解率（ORR）为97%，包括19%的完全缓解。del（17 p）/TP 53突变患者的ORR为100%，未突变IGHV患者为97%。36个月时无进展生存率为83%。最常见（>30%）的不良事件（任何级别）是腹泻（包括结肠炎）（64%）、皮疹（58%）、发热（42%）、恶心（38%）、寒战（36%）、咳嗽（33%）和疲劳（31%）。丙氨酸转氨酶/天冬氨酸转氨酶升高见于67%的患者（23% ≥ 3级）。Idelalisib和利妥昔单抗的组合是高度活性的，在初治的CLL老年患者中产生持久的疾病控制。这些结果支持了艾代拉里斯作为CLL初始治疗的进一步开发。
Idelalisib is a first-in-class oral inhibitor of PI3K delta that has shown substantial activity in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as initial therapy, 64 treatment-naive older patients with CLL or small lymphocytic leukemia (median age, 71 years; range, 65-90) were treated with rituximab 375mg/m(2) weekly x8 and idelalisib 150 mg twice daily continuously for 48 weeks. Patients completing 48 weeks without progression could continue to receive idelalisib on an extension study. The median time on treatment was 22.4 months (range, 0.8-45.81). The overall response rate (ORR) was 97%, including 19% complete responses. The ORR was 100% in patients with del(17p)/TP53 mutations and 97% in those with unmutated IGHV. Progression-free survival was 83% at 36 months. The most frequent (>30%) adverse events (any grade) were diarrhea (including colitis) (64%), rash (58%), pyrexia (42%), nausea (38%), chills (36%), cough (33%), and fatigue (31%). Elevated alanine transaminase/aspartate transaminase was seen in 67% of patients (23% grade >= 3). The combination of idelalisib and rituximab was highly active, resulting in durable disease control in treatment-naive older patients with CLL. These results support the further development of idelalisib as initial treatment of CLL.