毛状细胞白血病(HCL)对嘌呤类似物反应良好,总体中位无复发生存期为11-16年。大多数患者可以用相同或不同的嘌呤类似物进行再治疗,但是一部分患者会产生耐药性或累积毒性。新的药物,如Vemurafenib(BRAF激酶抑制剂),苯达莫司汀/利妥昔单抗(BR),Moxetumomabpasudotox(抗CD-22重组免疫毒素)和Ibrutinib在复发性HCL患者中具有新的作用。
五个数据库(PubMed,Embase,科克伦图书馆,WebofScienceandClinicalTrials.gov)使用以下搜索词进行搜索:“毛细胞白血病”或“白血病,毛细胞\"和\"复发\"或\"复发\"。我们仅包括具有结果数据的前瞻性临床试验。
Vemurafenib单药治疗在一项2期试验的两个独立分组中进行了评估。在美国手臂(n=24),ORR为100%(CR42%;PR58%)。在意大利的手臂(n=26),ORR为96%(CR35%;PR62%)。在第二阶段研究(n=25)中,维罗非尼和利妥昔单抗联合应用的CR为100%.BR的组合在70mg/m2(n=6)和90mg/m2(n=6)的苯达莫司汀剂量下分别实现100%的ORR,而CR为50%和67%。在第三阶段的审判中,莫沙莫单抗pasudotox(n=80)的ORR为75%(CR41%)。单剂伊鲁替尼(n=37)的ORR为54%。治疗通常耐受性良好。
新型药物在多次复发患者的HCL中具有良好的疗效。
Hairy cell leukemia (HCL) responds well to purine analogs with an overall median relapse free survival of 11-16 years. Most patients can be retreated with the same or a different purine analog however a subset of patients will become resistant or develop cumulative toxicities. Novel agents such as Vemurafenib (BRAF kinase inhibitor), Bendamustine/Rituximab (BR), Moxetumomab pasudotox (anti CD-22 recombinant immunotoxin) and Ibrutinib have emerging roles in patients with relapsed HCL.
Five databases (PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov) were searched using the following search terms: \"hairy cell leukemia\" or \"leukemia, hairy cell\" AND \"relapse\" or \"recurrence\". We included only prospective clinical trials with outcome data.
Vemurafenib monotherapy was evaluated in two separate arms of a phase 2 trial. In the US arm (n=24), the ORR was 100% (CR 42%; PR 58%). In the Italian arm (n=26), the ORR was 96% (CR 35%; PR 62%). In a phase 2 study (n=25), the combination of vemurafenib and rituximab showed CR of 100%. The combination of BR achieved an ORR of 100% whereas CR was 50% and 67% at a bendamustine dose of 70mg/m2 (n=6) and 90 mg/m2 (n=6) respectively. In a phase 3 trial, moxetumomab pasudotox (n=80) had an ORR of 75% (CR 41%). Single agent Ibrutinib (n=37) had an ORR of 54%. Therapies were generally well tolerated.
Novel agents have good efficacy in HCL in patients with multiple relapses.