Extended Treatment with Single-Agent Ibrutinib at the 420 mg Dose Leads to Durable Responses in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
Extended Treatment with Single-Agent Ibrutinib at the 420 mg Dose Leads to Durable Responses in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
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DOI：
10.1158/1078-0432.ccr-16-1431
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发表时间：
2017-03-01
期刊：
影响因子：
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通讯作者：
O'Brien S
中科院分区：
文献类型：
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作者：
Coutré SE;Furman RR;Flinn IW;Burger JA;Blum K;Sharman J;Jones J;Wierda W;Zhao W;Heerema NA;Johnson AJ;Tran A;Zhou C;Bilotti E;James DF;Byrd JC;O'Brien S
伊布替尼是一种一流的、每日一次的布鲁顿酪氨酸激酶口服抑制剂，可促进细胞凋亡，抑制B细胞增殖、粘附和迁移。在一项Ib/II期研究（PCYC-1102）中，已证明420和840 mg剂量的伊布替尼在初治（TN）或既往接受过≥1次治疗的复发性/难治性（R/R）CLL慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）患者中具有单药疗效和可接受的耐受性。随后，伊鲁替尼420 mg剂量在CLL中获得批准。我们报告了在PCYC-1102和长期扩展研究PCYC-1103中对94例TN和R/R CLL/SLL患者接受伊鲁替尼420 mg每日一次治疗的44个月随访数据。94例CLL/SLL患者（27例TN，67例R/R）接受了伊鲁替尼（420 mg/天）治疗。R/R疾病患者接受过中位4种既往治疗（范围，1-12）。反应迅速而持久，没有达到反应的中位持续时间。最佳总体缓解率为91%（85% TN [完全缓解（CR）26%]和94% R/R [9% CR]）。两组均未达到中位无进展生存期（PFS）。TN和R/R患者的30个月PFS率分别为96%和76%。随着随访时间的延长，伊布替尼的耐受性良好; ≥3级血细胞减少和疲劳的发生率以及因毒性而停药的发生率随时间推移而降低。在TN和R/R CLL/SLL患者中，420 mg每日一次单药伊曲替尼可产生持久缓解，且耐受性良好，随访长达44个月。目前，66%的患者继续使用伊鲁替尼。
Ibrutinib, a first-in-class, once-daily, oral inhibitor of Bruton’s tyrosine kinase, promotes apoptosis, and inhibits B-cell proliferation, adhesion, and migration. Ibrutinib has demonstrated single-agent efficacy and acceptable tolerability at doses of 420 and 840 mg in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who were treatment naïve (TN) or had relapsed/refractory (R/R) CLL after ≥1 prior therapy in a phase 1b/2 study (PCYC-1102). Subsequently, the ibrutinib 420 mg dose was approved in CLL. We report data with 44 months of follow-up on 94 patients with TN and R/R CLL/SLL receiving ibrutinib 420 mg once-daily in PCYC-1102 and the long-term extension study PCYC-1103. Ninety-four CLL/SLL patients (27 TN, 67 R/R) were treated with ibrutinib (420 mg/day). Patients with R/R disease had received a median of 4 prior therapies (range, 1–12). Responses were rapid and durable and median duration of response was not reached. Best overall response was 91% (85% TN [complete response (CR) 26%] and 94% R/R [9% CR]). Median progression-free survival (PFS) was not reached in either group. The 30-month PFS rate was 96% and 76% for TN and R/R patients, respectively. Ibrutinib was well tolerated with extended follow-up; rates of grade ≥3 cytopenias and fatigue, as well as discontinuations due to toxicities decreased over time. Single-agent ibrutinib at 420 mg once-daily resulted in durable responses and was well tolerated with up to 44 months follow-up in patients with TN and R/R CLL/SLL. Presently, 66% of patients continue on ibrutinib.