Complex karyotype is a stronger predictor than del(17p) for an inferior outcome in relapsed or refractory chronic lymphocytic leukemia patients treated with ibrutinib-based regimens.
Complex karyotype is a stronger predictor than del(17p) for an inferior outcome in relapsed or refractory chronic lymphocytic leukemia patients treated with ibrutinib-based regimens.
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DOI：
10.1002/cncr.29566
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发表时间：
2015-10-15
期刊：
影响因子：
6.2
通讯作者：
Keating MJ
中科院分区：
文献类型：
--
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
伊布替尼在复发性/难治性（R/R）CLL患者中具有活性。在接受伊布替尼治疗R/R CLL的患者中，尽管初始缓解率相当，但通过间期荧光原位杂交（FISH）鉴定的del（17 p）与较差的无进展生存期相关。Del（17 p）通常与复杂中期核型（CKT）相关;尚未报告CKT在伊鲁替尼治疗患者中的预后意义。我们回顾了2010年至2013年在MD安德森癌症中心接受基于伊替尼的研究性方案治疗的88例R/R CLL患者。对骨髓进行处理前FISH和脂多糖刺激的中期细胞遗传学分析。56/88例患者的治疗前中期染色体核型充足。56例中有21例核型复杂，FISH检测有17例缺失（17 p）。包括部分缓解伴持续性淋巴细胞增多在内的总缓解率为94%，完全缓解率为17%。在多变量分析（MVA）中，仅CKT与无事件生存期（EFS）显著相关[HR 6.6（1.7-25.6），p=0.006]。氟达拉滨难治性CLL [HR 6.9（1.8-27.1），p=0.005]和CKT [HR 5.9（1.6-22.2），p=0.008]与MVA中较差的总生存期（OS）独立相关。FISH检测的Del（17 p）与MVA的EFS或OS无显著相关性。CKT是伊匹替尼治疗的R/R CLL患者结局的有力预测因子，可能是比FISH检测的del（17 p）更强的生物学行为预测因子。鉴于其相对较差的结果，CKT患者是巩固治疗策略或新型治疗组合研究的理想候选人。
Ibrutinib is active in patients with relapsed/refractory (R/R) CLL. In patients treated with ibrutinib for R/R CLL, del(17p) identified by interphase fluorescence in situ hybridization (FISH) is associated with inferior progression-free survival, despite equivalent initial response rates. Del(17p) is frequently associated with complex metaphase karyotype (CKT); the prognostic significance of CKT in ibrutinib-treated patients has not been reported. We reviewed 88 patients treated for R/R CLL at MD Anderson Cancer Center with investigational ibrutinib-based regimens from 2010–2013. Pre-treatment FISH and Lipopolysaccharide-stimulated metaphase cytogenetic analysis were performed on bone marrow. Adequate pre-treatment metaphase karyotype was available for 56/88 patients. Karyotype was complex in 21 of 56 cases; 17 of the 21 had del(17p) by FISH. Overall response rate, including partial remission with persistent lymphocytosis, was 94% with 17% complete responses. In multivariable analysis (MVA), only CKT was significantly associated with event-free survival (EFS) [HR 6.6 (1.7–25.6), p=0.006]. Fludarabine-refractory CLL [HR 6.9 (1.8–27.1), p=0.005] and CKT [HR 5.9 (1.6–22.2), p=0.008] were independently associated with inferior overall survival (OS) in MVA. Del(17p) by FISH was not significantly associated with EFS or OS in MVA. CKT is a powerful predictor of outcome in ibrutinib-treated patients with R/R CLL and may be a stronger predictor of biological behavior than del(17p) by FISH. Given their relatively poor outcomes, patients with CKT are ideal candidates for studies of consolidative treatment strategies or novel treatment combinations.