Toxicities and outcomes of 616 ibrutinib-treated patients in the United States: a real-world analysis.
Toxicities and outcomes of 616 ibrutinib-treated patients in the United States: a real-world analysis.
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DOI：
10.3324/haematol.2017.182907
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发表时间：
2018-05
期刊：
影响因子：
10.1
通讯作者：
Ujjani CS
中科院分区：
文献类型：
--
作者：
Mato AR;Nabhan C;Thompson MC;Lamanna N;Brander DM;Hill B;Howlett C;Skarbnik A;Cheson BD;Zent C;Pu J;Kiselev P;Goy A;Claxton D;Isaac K;Kennard KH;Timlin C;Landsburg D;Winter A;Nasta SD;Bachow SH;Schuster SJ;Dorsey C;Svoboda J;Barr P;Ujjani CS
导致伊布鲁替尼被批准用于治疗慢性淋巴细胞白血病的临床试验表明，它的副作用与传统化疗不同。临床实践中中止的原因还没有得到充分的研究。我们对伊布鲁替尼用于商业或临床试验的慢性淋巴细胞白血病患者进行了回顾性分析。我们的目标是比较在两种情况下报告的毒性的类型和频率，评估停药率，并评估结果。这项多中心的回顾性分析包括9个美国癌症中心或Connect®慢性淋巴细胞性白血病登记中心的接受伊布鲁替尼治疗的慢性淋巴细胞白血病患者。我们检查了人口统计学、剂量、停药率和原因、毒性和结果。主要终点是无进展生存期。确定了616名接受伊布鲁替尼治疗的患者。共有546名患者(88%)接受了商业药物的治疗。临床试验患者更年轻(平均年龄58岁对61岁，P=0.01)，从诊断到使用伊布鲁替尼治疗的时间相似(平均85个月对87个月，P=0.8)。平均随访17个月，估计有41%的患者停止使用ibrutinib(停止使用ibrutinib的中位时间为7个月)。值得注意的是，ibrutinib毒性是在所有情况下停止使用的最常见原因。整个队列的中位无进展生存期和总生存期分别为35个月和未达到(中位随访17个月)。在关于伊布鲁替尼治疗慢性淋巴细胞白血病患者的最大报道系列中，我们显示41%的患者停用伊布鲁替尼。不耐受而不是慢性淋巴细胞性白血病进展是停药的最常见原因。结果仍然很好，不受治疗路线或患者是否接受临床研究或商业治疗的影响。这些数据强烈支持找到将伊布鲁替尼不耐受降至最低的策略，以便进一步最大化疗效。未来的临床试验应该考虑时间限制的治疗方法，特别是在获得完全反应的患者中，以便将伊布鲁替尼的暴露降至最低。
Clinical trials that led to ibrutinib’s approval for the treatment of chronic lymphocytic leukemia showed that its side effects differ from those of traditional chemotherapy. Reasons for discontinuation in clinical practice have not been adequately studied. We conducted a retrospective analysis of chronic lymphocytic leukemia patients treated with ibrutinib either commercially or on clinical trials. We aimed to compare the type and frequency of toxicities reported in either setting, assess discontinuation rates, and evaluate outcomes. This multicenter, retrospective analysis included ibrutinib-treated chronic lymphocytic leukemia patients at nine United States cancer centers or from the Connect® Chronic Lymphocytic Leukemia Registry. We examined demographics, dosing, discontinuation rates and reasons, toxicities, and outcomes. The primary endpoint was progression-free survival. Six hundred sixteen ibrutinib-treated patients were identified. A total of 546 (88%) patients were treated with the commercial drug. Clinical trial patients were younger (mean age 58 versus 61 years, P=0.01) and had a similar time from diagnosis to treatment with ibrutinib (mean 85 versus 87 months, P=0.8). With a median follow-up of 17 months, an estimated 41% of patients discontinued ibrutinib (median time to ibrutinib discontinuation was 7 months). Notably, ibrutinib toxicity was the most common reason for discontinuation in all settings. The median progression-free survival and overall survival for the entire cohort were 35 months and not reached (median follow-up 17 months), respectively. In the largest reported series on ibrutinib- treated chronic lymphocytic leukemia patients, we show that 41% of patients discontinued ibrutinib. Intolerance as opposed to chronic lymphocytic leukemia progression was the most common reason for discontinuation. Outcomes remain excellent and were not affected by line of therapy or whether patients were treated on clinical studies or commercially. These data strongly argue in favor of finding strategies to minimize ibrutinib intolerance so that efficacy can be further maximized. Future clinical trials should consider time-limited therapy approaches, particularly in patients achieving a complete response, in order to minimize ibrutinib exposure.
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影响因子：
6.2
作者：
Thompson PA;O'Brien SM;Wierda WG;Ferrajoli A;Stingo F;Smith SC;Burger JA;Estrov Z;Jain N;Kantarjian HM;Keating MJ
通讯作者：
Keating MJ
影响因子：
6.2
作者：
Jain P;Thompson PA;Keating M;Estrov Z;Ferrajoli A;Jain N;Kantarjian H;Burger JA;O'Brien S;Wierda WG
通讯作者：
Wierda WG
影响因子：
20.3
作者：
Lampson, Benjamin L.;Kasar, Siddha N.;Brown, Jennifer R.
通讯作者：
Brown, Jennifer R.
影响因子：
45.3
作者：
Woyach, Jennifer A.;Ruppert, Amy S.;Byrd, John C.
通讯作者：
Byrd, John C.
影响因子：
10.1
作者：
Winqvist, Maria;Asklid, Anna;Osterborg, Anders
通讯作者：
Osterborg, Anders