Postibrutinib outcomes in patients with mantle cell lymphoma
Postibrutinib outcomes in patients with mantle cell lymphoma
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DOI：
10.1182/blood-2015-10-673145
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发表时间：
2016-03-24
期刊：
影响因子：
20.3
通讯作者：
Blum, Kristie A.
中科院分区：
文献类型：
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作者：
Martin, Peter;Maddocks, Kami;Blum, Kristie A.
尽管在套细胞淋巴瘤（MCL）中具有前所未有的临床活性，但对伊鲁替尼的原发性和获得性耐药很常见。对于经历伊鲁替尼失败的患者的结局和理想管理尚不清楚。我们在15个国际研究中心对所有在接受伊曲替尼治疗期间发生疾病进展的MCL患者进行了回顾性队列研究。对病历的临床特征、病理学和放射学数据以及替尼治疗前和治疗后使用的治疗进行了评价。共有114例受试者符合合格性标准。中位既往治疗次数为3次（范围：0-10次）。伊布替尼治疗开始时，46%、31%和23%的患者的套细胞淋巴瘤国际预后指数（MIPI）评分分别为低、中等和高。在接受伊替尼和普替尼治疗前有可用数据的患者中，47名患者中有34名和12名患者中有11名Ki 67> 30%。伊鲁替尼的中位时间为4.7个月（范围0.7-43.6）。停用伊鲁替尼后的中位总生存期（OS）为2.9个月（95%置信区间[ CI]，1.6-4.9）。在104例有数据可用的患者中，73例在停用伊鲁替尼后平均0.3个月接受后续治疗，中位OS为5.8个月（95% CI，3.7-10.4）。多变量考克斯回归分析的MIPI后替尼治疗，并随后与苯达莫司汀，阿糖胞苷，或来那度胺治疗未能揭示任何与OS的关联。不良的临床结果中指出，在大多数患者原发或继发性伊布替尼耐药。我们无法确定明显改善结果的治疗方法。未来的试验应侧重于了解伊鲁替尼耐药的机制和伊鲁替尼后的治疗。
Despite unprecedented clinical activity in mantle cell lymphoma (MCL), primary and acquired resistance to ibrutinib is common. The outcomes and ideal management of patients who experience ibrutinib failure are unclear. We performed a retrospective cohort study of all patients with MCL who experienced disease progression while receiving ibrutinib across 15 international sites. Medical records were evaluated for clinical characteristics, pathological and radiological data, and therapies used pre- and postibrutinib. A total of 114 subjects met eligibility criteria. The median number of prior therapies was 3 (range, 0-10). The Mantle Cell Lymphoma International Prognostic Index (MIPI) scores at the start of ibrutinib were low, intermediate, and high in 46%, 31%, and 23% of patients, respectively. Of patients with available data prior to ibrutinib and postibrutinib, 34 of 47 and 11 of 12 had a Ki67 >30%. The median time on ibrutinib was 4.7 months (range 0.7-43.6). The median overall survival (OS) following cessation of ibrutinib was 2.9 months (95% confidence interval [ CI], 1.6-4.9). Of the 104 patients with data available, 73 underwent subsequent treatment an average of 0.3 months after stopping ibrutinib with a median OS of 5.8 months (95% CI, 3.7-10.4). Multivariate Cox regression analysis of MIPI before postibrutinib treatment, and subsequent treatment with bendamustine, cytarabine, or lenalidomide failed to reveal any association with OS. Poor clinical outcomes were noted in the majority of patients with primary or secondary ibrutinib resistance. We could not identify treatments that clearly improved outcomes. Future trials should focus on understanding the mechanisms of ibrutinib resistance and on treatment after ibrutinib.