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塞利尼索、硼替佐米与地塞米松:一种用于多次治疗的骨髓瘤患者的有效挽救方案。

Selinexor, Bortezomib and Dexamethasone: An Effective Salvage Regimen for Heavily Pretreated Myeloma Patients.

作者信息

Delforge Michel, Raddoux Jolien, Antonis Corine, Clement Céline, Kint Nicolas, Vanhellemont Anneleen, Bravetti Julie, Vandenberghe Peter

机构信息

Department of Hematology, University Hospital Leuven, Leuven, Belgium.

Karyopharm Therapeutics, Newton, MA, USA.

出版信息

Onco Targets Ther. 2022 Mar 14;15:243-250. doi: 10.2147/OTT.S341120. eCollection 2022.

Abstract

PURPOSE

Multiple myeloma (MM) patients with triple- and penta-refractory disease have a poor survival and limited treatment options. Selinexor, in combination with bortezomib and dexamethasone, demonstrated clinical activity in the STOMP study as well as in the BOSTON study in previously treated patients with disease refractory to a proteasome inhibitor (PI).

PATIENTS AND METHODS

Here, we report a real-world case series of 7 heavily pretreated MM patients who had been extensively pretreated with bortezomib and had disease refractory to PIs, including carfilzomib; who were administered a starting dose of 100 mg of selinexor, 20-40 mg dexamethasone and 1.3 mg/m of bortezomib, each once weekly. The majority of these patients (6 patients, 86.0%) had penta-refractory disease, with 5 patients (71.4%) having disease refractory to bortezomib and carfilzomib, and all 7 patients having pomalidomide refractory disease. The median number of prior lines of therapy was 8 (range 4-12).

RESULTS

The seven patients in this case series received selinexor for a median of 5 cycles (range 1-10). Four patients (57.1%) had a dose reduction of selinexor. Five patients (71.4%) had a response, of which 2 (29.0%) had a very good partial response (VGPR) and 3 (43.0%) had a partial response (PR). One patient (14.3%) had stable disease (SD) and 1 (14.3%) had progressive disease (PD). There were no new safety signals.

CONCLUSION

The selinexor, bortezomib, and dexamethasone triplet combination demonstrates activity in PI-resistant MM and patients with heavily pretreated MM with refractory disease and after multiple lines of therapy.

摘要

目的

患有三重难治和五重难治性疾病的多发性骨髓瘤(MM)患者生存情况不佳且治疗选择有限。在STOMP研究以及BOSTON研究中,塞利尼索联合硼替佐米和地塞米松,在先前接受过蛋白酶体抑制剂(PI)治疗的难治性疾病患者中显示出临床活性。

患者与方法

在此,我们报告了一个真实世界的病例系列,包括7例接受过大量治疗的MM患者,这些患者曾广泛接受硼替佐米治疗且对包括卡非佐米在内的PI难治;给予他们起始剂量为100mg塞利尼索、20 - 40mg地塞米松和1.3mg/m²硼替佐米,每周一次。这些患者中的大多数(6例,86.0%)患有五重难治性疾病,5例(71.4%)对硼替佐米和卡非佐米难治,所有7例患者对泊马度胺难治。既往治疗线数的中位数为8(范围4 - 12)。

结果

该病例系列中的7例患者接受塞利尼索治疗的中位数为5个周期(范围1 - 10)。4例患者(57.1%)减少了塞利尼索剂量。5例患者(71.4%)有反应,其中2例(29.0%)获得非常好的部分缓解(VGPR),3例(43.0%)获得部分缓解(PR)。1例患者(14.3%)疾病稳定(SD),1例(14.3%)疾病进展(PD)。没有新的安全信号。

结论

塞利尼索、硼替佐米和地塞米松三联组合在PI耐药的MM以及接受过大量治疗且患有难治性疾病并经过多线治疗的MM患者中显示出活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba9/8932935/11a03f336ba2/OTT-15-243-g0001.jpg

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