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塞利尼索治疗复发或难治性多发性骨髓瘤患者。

Selinexor for the treatment of patients with relapsed or refractory multiple myeloma.

机构信息

Khyber Girls Medical College, Peshawar, Pakistan.

Khyber Medical College, Peshawar, Pakistan.

出版信息

J Oncol Pharm Pract. 2024 Apr;30(3):535-546. doi: 10.1177/10781552241235902. Epub 2024 Mar 8.

Abstract

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.

DATA SOURCE

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.

DATA SUMMARY

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%.

CONCLUSION

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.

摘要

目的

多发性骨髓瘤细胞由于过度表达转运蛋白 exportin 1 而对标准疗法产生耐药性。Selinexor 是一种新型药物,可靶向这些细胞中的 Exportin 1 蛋白。

资料来源

进行了全面检索,并使用 PubMed、Google Scholar 和 clincialtrials.gov 收集了显示 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。

资料概要

包括 STORM、BOSTON 和 STOMP 临床试验的结果。STORM 试验的第 I 部分和第 II 部分分别显示无进展生存期(PFS)为 4.7 个月和 3.7 个月,中位反应持续时间为 6.2 个月和 4.4 个月,总生存期分别为 7.3 个月和 8.4 个月。BOSTON 试验的 SVd 臂(selinexor、硼替佐米和地塞米松)的中位随访时间为 13.2 个月,mPFS 为 13.93 个月。Vd 臂(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 试验仍在进行中,可用数据有限。SKd 臂(selinexor、卡非佐米和地塞米松)在三重难治性多发性骨髓瘤患者中的总缓解率为 66.7%,在高危细胞遗传学患者中的总缓解率为 82%。SPd 臂(selinexor、泊马度胺和地塞米松)在泊马度胺初治-非难治性患者中的总缓解率为 54.30%,在泊马度胺难治性患者中的总缓解率为 35.70%,在 RP2D 剂量下患者的总缓解率为 60%。SRd 臂(selinexor、来那度胺和地塞米松)在来那度胺初治患者中的总缓解率为 91.7%,在来那度胺难治性患者中的总缓解率为 12.5%。SVd(selinexor、硼替佐米和地塞米松)臂在所有患者中的总缓解率为 63%,而 SDd 臂(selinexor、达雷妥尤单抗和地塞米松)的总缓解率为 73%。

结论

为了改善复发性/难治性多发性骨髓瘤患者的预后,开发新的疗法、评估潜在的治疗协同作用以及通过确定多发性骨髓瘤疗法在多个疾病亚组中的疗效来克服耐药性至关重要。

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