Single-agent ibrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia: a 5-year experience
Single-agent ibrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia: a 5-year experience
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DOI：
10.1182/blood-2017-10-810044
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发表时间：
2018-04-26
期刊：
影响因子：
20.3
通讯作者：
Byrd, John C.
中科院分区：
文献类型：
--
作者：
O'Brien, Susan;Furman, Richard R.;Byrd, John C.
我们此前报道了伊布鲁替尼对治疗初治的老年患者(65岁)和复发/难治(R/R)慢性淋巴细胞性白血病/小淋巴细胞性淋巴瘤(CLL/SLL)患者的持久反应和可管理的安全性。现在，我们报告了在患有TN(N=31)和R/R(N=101)CLL/SLL的患者群体中的长期有效性和安全性，平均随访时间为5年。在目前的5年随访中，ibrutinib继续产生89%的高总有效率，随着时间的推移，TN患者的完全有效率增加到29%，R/R患者的完全有效率增加到10%。TN患者未达到中位无进展生存期(PFS)。5年PFS率TN组为92%，R/R组为44%。R/R患者的中位PFS为51个月，del(11q)、del(17p)和未突变IGHV患者的中位PFS分别为51、26和43个月，这表明伊布鲁替尼在一些高危亚组中具有长期疗效。Del(17p)的R/R患者和先前接受更多治疗的R/R患者的生存结果较差。随着时间的推移，中性粒细胞减少症和血小板减少症等3级细胞减少症的发病逐渐减少。与随后的时期相比，限制治疗的不良事件在第一年更为频繁。这些结果证明了ibrutinib在较长时间内的持续疗效和可接受的耐受性，为Bruton酪氨酸激酶抑制剂治疗慢性淋巴细胞白血病/系统性红斑狼疮患者提供了最长的经验。
We previously reported durable responses and manageable safety of ibrutinib from a 3-year follow-up of treatment-naive (TN) older patients (>= 65 years of age) and relapsed/refractory (R/R) patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We now report on long-term efficacy and safety with median follow-up of 5 years in this patient population with TN (N = 31) and R/R (N = 101) CLL/SLL. With the current 5-year follow-up, ibrutinib continues to yield a high overall response rate of 89%, with complete response rates increasing over time to 29% in TN patients and 10% in R/R patients. The median progression-free survival (PFS) was not reached in TN patients. The 5-year PFS rate was 92% in TN patients and 44% in R/R patients. Median PFS in R/R patients was 51 months; in those with del(11q), del(17p), and unmutated IGHV, it was 51, 26, and 43 months, respectively, demonstrating long-term efficacy of ibrutinib in some highrisk subgroups. Survival outcomes were less robust for R/R patients with del(17p) and those who received more prior therapies. The onset of grade >= 3 cytopenias, such as neutropenia and thrombocytopenia, decreased over time. Treatment-limiting adverse events were more frequent during the first year compared with subsequent periods. These results demonstrate sustained efficacy and acceptable tolerability of ibrutinib over an extended time, providing the longest experience for Bruton tyrosine kinase inhibitor treatment in patients with CLL/SLL.