Patients with mantle cell lymphoma failing ibrutinib are unlikely to respond to salvage chemotherapy and have poor outcomes
Patients with mantle cell lymphoma failing ibrutinib are unlikely to respond to salvage chemotherapy and have poor outcomes
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DOI：
10.1093/annonc/mdv111
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发表时间：
2015-06-01
影响因子：
50.5
通讯作者：
Wang, M. L.
中科院分区：
文献类型：
--
作者：
Cheah, C. Y.;Chihara, D.;Wang, M. L.
背景资料：尽管伊曲替尼在复发/难治性套细胞淋巴瘤（MCL）患者中非常有效，但相当大比例的患者患有耐药疾病。患者和方法：我们进行了一项回顾性研究，所有患者MCL治疗与伊鲁替尼在MD安德森癌症中心2011年1月至2014年1月之间使用药房和临床数据库。因任何原因而停用伊鲁替尼的患者均被纳入研究。结果：我们确定了42例MCL患者，他们因治疗中的疾病进展（n = 28）、毒性（n = 6）、缓解期的择期干细胞移植（n = 4）或撤回同意（n = 4）而停用治疗。中位年龄为69岁，35例（83%）为男性;既往治疗的中位次数为2次（范围1-8），从首次诊断MCL至开始使用伊鲁替尼的中位时间为3.0年（范围0.5-15.5）。患者接受了中位数为6.5（范围1-43）个周期的伊曲替尼治疗。在31例接受伊鲁替尼治疗后出现疾病进展并接受挽救治疗的患者中，总体缓解率和完全缓解率分别为32%和19%。在停用伊鲁替尼后中位随访10.7（范围2.4-38.9）个月后，疾病进展患者的中位总生存期（OS）为8.4个月。通过单变量分析，进展时血清乳酸脱氢酶升高与较差的OS.Conclusion：MCL患者在接受伊曲替尼治疗后出现疾病进展的结局较差，对挽救治疗的应答率较低，应答持续时间较短。迫切需要进一步的研究来更好地了解和克服伊鲁替尼耐药性。
Background: Although ibrutinib is highly effective in patients with relapsed/refractory mantle cell lymphoma (MCL), a substantial proportion of patients have resistant disease. The subsequent outcomes of such patients are unknown.Patients and methods: We carried out a retrospective review of all patients with MCL treated with ibrutinib at MD Anderson Cancer Center between January 2011 and January 2014 using pharmacy and clinical databases. Patients who had discontinued ibrutinib for any reason were included in the study.Results: We identified 42 patients with MCL who discontinued therapy due to disease progression on treatment (n = 28), toxicity (n = 6), elective stem-cell transplant in remission (n = 4) or withdrawn consent (n = 4). The median age was 69 years, 35 (83%) were male; the median number of prior treatments was 2 (range 1-8) and the median time from initial diagnosis of MCL to commencing ibrutinib was 3.0 (range 0.5-15.5) years. Patients had received a median of 6.5 (range 1-43) cycles of ibrutinib. Among 31 patients who experienced disease progression following ibrutinib and underwent salvage therapy, the overall and complete response rates were 32% and 19%, respectively. After a median follow-up of 10.7 (range 2.4-38.9) months from discontinuation of ibrutinib, the median overall survival (OS) among patients with disease progression was 8.4 months. By univariate analysis, elevated serum lactate dehydrogenase at progression was associated with inferior OS.Conclusion: The outcome of patients with MCL who experience disease progression following ibrutinib therapy is poor, with both low response rates to salvage therapy and short duration of responses. Further studies to better understand and overcome ibrutinib resistance are urgently needed.