目的:多发性骨髓瘤细胞由于转运蛋白的过度表达而抵抗标准疗法,出口1。Selinexor是一种靶向这些细胞中的Exportin1蛋白的新型药物。
方法:进行了全面搜索,使用PubMed收集显示selinexor在复发性/难治性多发性骨髓瘤中的疗效和安全性的数据,谷歌学者,和clincialtrials.gov
方法:来自STORM临床试验的结果,波士顿,包括STOMP。STORM试验的第一部分和第二部分显示无进展生存期(PFS)为4.7和3.7个月,中位反应持续时间为6.2个月和4.4个月,总生存期为7.3和8.4个月,分别。波士顿试验的SVd手臂(selinexor,硼替佐米,和地塞米松)的中位随访期为13.2个月,mPFS为13.93个月。Vd组(硼替佐米和地塞米松)的中位随访时间为16.5个月,mPFS为9.46个月。STOMP试验仍然有效,可用数据有限。SKD手臂(selinexor,Carfilzomib,和地塞米松)报告三联难治性多发性骨髓瘤患者的总反应率为66.7%,和82%的高风险细胞遗传学患者。SPd手臂(selinexor,泊马度胺,和地塞米松)显示泊马度胺的总缓解率为54.30%,难治性泊马度胺为35.70%,RP2D剂量为60%。SRd手臂(selinexor,来那度胺,和地塞米松)显示来那度胺初治患者的总缓解率为91.7%,来那度胺难治性患者的总缓解率为12.5%。SVd(selinexor,硼替佐米,和地塞米松)组报告所有患者的总反应率为63%,而SDd组(selinexor,daratumumab,和地塞米松)显示总反应率为73%。
结论:为了改善复发/难治性多发性骨髓瘤患者的预后,开发新的疗法至关重要,评估潜在的治疗协同作用,并通过确定多个疾病亚组的多发性骨髓瘤治疗的疗效来克服耐药性。
OBJECTIVE: Multiple myeloma cells resist standard therapies due to overexpression of the transport protein, exportin 1. Selinexor is a novel drug that targets the Exportin 1 protein in these cells.
METHODS: A comprehensive search was done, and data showing the efficacy and safety of selinexor in relapsed/refractory multiple myeloma was collected using PubMed, Google Scholar, and clincialtrials.gov.
METHODS: Results from the clinical trials STORM, BOSTON, and STOMP were included. Parts I and II of the STORM trial revealed a progression-free survival (PFS) of 4.7 and 3.7 months, a median duration of response of 6.2 and 4.4 months, and an overall survival of 7.3 and 8.4 months, respectively. BOSTON trial\'s SVd arm (selinexor, bortezomib, and dexamethasone) had a median follow-up period of 13.2 months and an mPFS of 13.93 months. The Vd arm (bortezomib and dexamethasone) had a median follow-up duration of 16.5 months and an mPFS of 9.46 months. The STOMP trial is still active and has limited data available. The SKd arm (selinexor, carfilzomib, and dexamethasone) reported an overall response rate of 66.7% in patients with triple refractory multiple myeloma, and 82% in patients with high-risk cytogenetics. The SPd arm (selinexor, pomalidomide, and dexamethasone) shows an overall response rate of 54.30% in pomalidomide naïve-nonrefractory, 35.70% in pomalidomide refractory and 60% in those dosed at RP2D. SRd arm (selinexor, lenalidomide, and dexamethasone) shows an overall response rate of 91.7% in lenalidomide naïve and 12.5% in lenalidomide refractory patients. SVd (selinexor, bortezomib, and dexamethasone) arm reported an overall response rate of 63% in all patients while the SDd arm (selinexor, daratumumab, and dexamethasone) showed an overall response rate of 73%.
CONCLUSIONS: To improve the outcome of patients with relapsed/refractory multiple myeloma, it is critical to develop new therapies, assess potential therapeutic synergies, and overcome drug resistance by determining the efficacy of multiple myeloma therapies across multiple disease subgroups.