Long-term outcomes for patients with chronic lymphocytic leukemia who discontinue ibrutinib.
Long-term outcomes for patients with chronic lymphocytic leukemia who discontinue ibrutinib.
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DOI：
10.1002/cncr.30596
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发表时间：
2017-06-15
期刊：
影响因子：
6.2
通讯作者：
Wierda WG
中科院分区：
文献类型：
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作者：
Jain P;Thompson PA;Keating M;Estrov Z;Ferrajoli A;Jain N;Kantarjian H;Burger JA;O'Brien S;Wierda WG
伊布替尼是一种布鲁顿酪氨酸激酶（BTK）抑制剂，获批用于一线和复发难治性慢性淋巴细胞白血病患者的治疗。我们以前报道过停用伊鲁替尼的患者预后不良;然而，长期预后未报道。我们回顾性分析了2010年至2015年在M.D.进行的320例接受伊鲁替尼治疗的患者的临床研究数据。安德森癌症中心。我们报告了CLL患者停用伊鲁替尼后的长期结局。总计320例（28%）接受以伊鲁替尼为基础的方案治疗的患者中，90例患者停用了伊鲁替尼。80例患者为复发性/难治性，10例为初治患者。至停药的中位时间为15个月（范围1.2-54）。在开始使用伊鲁替尼后中位随访38个月后，40名患者（44%）存活。停用伊鲁替尼的主要原因是不耐受，n=29（32%）;其他，n=28（31%）;进展，n=19（21%）;和里希特转化（RT），n=9（10%）。中位生存期为33个月的伊鲁替尼不耐受，11个月的其他原因，16个月的进展性CLL和：2个月的RT。在19例进展性CLL患者中，42%的后续治疗反应。在治疗期间观察到停用伊布替尼。发生疾病转化的患者预后尤其差，而接受伊曲替尼治疗后发生疾病进展的患者的中位生存期<1.5年。生存率与停药原因相关;与疾病转化相比，进展性CLL患者的生存率更高。对于在伊鲁替尼治疗中进展的CLL患者，有效的挽救策略至关重要。
Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor, approved for the treatment of patients with chronic lymphocytic leukemia in frontline and relapsed-refractory settings. We previously reported poor outcomes for patients discontinuing ibrutinib; however, long term outcomes were not reported. We retrospectively analyzed data for 320 patients treated with ibrutinib on clinical studies between 2010–15 at M.D. Anderson Cancer Center. We report long-term outcomes for CLL patients after discontinuing ibrutinib. Ninety patients discontinued ibrutinib from a total of 320 patients (28%) treated with ibrutinib-based regimens. Eighty patients were relapsed/refractory and 10 were treatment-naïve. The median time to discontinuation was 15 months (range 1.2–54). After a median follow up of 38 months from initiating ibrutinib, 40 patients (44%) were alive. Major reasons for ibrutinib discontinuation were intolerance, n=29 (32%); miscellaneous n=28 (31%); progression, n=19 (21%); and Richter’s Transformation (RT), n=9 (10%). Median survival was 33 months for ibrutinib intolerance; 11 months for miscellaneous causes, 16 months for progressive CLL and: 2 months for RT. Among the 19 patients with progressive CLL, 42% responded to subsequent therapy. Ibrutinib discontinuation is observed during therapy. Patients with disease transformation have especially poor outcomes, while patients who develop progressive disease on ibrutinib therapy have a median survival of <1.5 years. Survival was associated with reason for discontinuation; patients with progressive CLL had better survival compared to disease transformation. Effective salvage strategies for patients with CLL who progress on ibrutinib therapy is of critical importance.
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影响因子：
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作者：
Sharma S;Galanina N;Guo A;Lee J;Kadri S;Van Slambrouck C;Long B;Wang W;Ming M;Furtado LV;Segal JP;Stock W;Venkataraman G;Tang WJ;Lu P;Wang YL
通讯作者：
Wang YL
推动CLL的突变及其在进展和复发中的演变。
影响因子：
64.8
作者：
Landau DA;Tausch E;Taylor-Weiner AN;Stewart C;Reiter JG;Bahlo J;Kluth S;Bozic I;Lawrence M;Böttcher S;Carter SL;Cibulskis K;Mertens D;Sougnez CL;Rosenberg M;Hess JM;Edelmann J;Kless S;Kneba M;Ritgen M;Fink A;Fischer K;Gabriel S;Lander ES;Nowak MA;Döhner H;Hallek M;Neuberg D;Getz G;Stilgenbauer S;Wu CJ
通讯作者：
Wu CJ
慢性淋巴细胞白血病患者对 BTK 抑制产生耐药性的克隆进化
影响因子：
16.6
作者：
Burger JA;Landau DA;Taylor-Weiner A;Bozic I;Zhang H;Sarosiek K;Wang L;Stewart C;Fan J;Hoellenriegel J;Sivina M;Dubuc AM;Fraser C;Han Y;Li S;Livak KJ;Zou L;Wan Y;Konoplev S;Sougnez C;Brown JR;Abruzzo LV;Carter SL;Keating MJ;Davids MS;Wierda WG;Cibulskis K;Zenz T;Werner L;Dal Cin P;Kharchencko P;Neuberg D;Kantarjian H;Lander E;Gabriel S;O'Brien S;Letai A;Weitz DA;Nowak MA;Getz G;Wu CJ
通讯作者：
Wu CJ
DOI：
10.1056/nejmoa1400029
发表时间：
2014-06-12
期刊：
The New England journal of medicine
影响因子：
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作者：
Woyach JA;Furman RR;Liu TM;Ozer HG;Zapatka M;Ruppert AS;Xue L;Li DH;Steggerda SM;Versele M;Dave SS;Zhang J;Yilmaz AS;Jaglowski SM;Blum KA;Lozanski A;Lozanski G;James DF;Barrientos JC;Lichter P;Stilgenbauer S;Buggy JJ;Chang BY;Johnson AJ;Byrd JC
通讯作者：
Byrd JC
影响因子：
20.3
作者：
Ahn, Inhye E.;Underbayev, Chingiz;Wiestner, Adrian
通讯作者：
Wiestner, Adrian