Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma
Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma
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DOI：
10.1182/blood-2018-06-858852
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发表时间：
2018-12-13
期刊：
影响因子：
20.3
通讯作者：
Chen, Christine
中科院分区：
文献类型：
--
作者：
Bahlis, Nizar J.;Sutherland, Heather;Chen, Christine
Selinexor是核输出蛋白Exportin 1的口服抑制剂。临床前研究表明，通过抑制NF-κ B信号传导和肿瘤抑制蛋白的核保留，selinexor和蛋白酶体抑制剂（PI）之间具有协同抗骨髓瘤活性。我们测试了selinexor联合低剂量硼替佐米和地塞米松（SVd）治疗复发性或难治性多发性骨髓瘤（MM）。本研究的主要目的是确定SVd的安全性特征、总缓解率（ORR）和推荐的II期剂量（RP 2D）。我们招募了42名患者，接受selinexor（60，80或100 mg口服）+硼替佐米（1.3 mg/m2皮下注射）和地塞米松（20 mg口服）每周一次或两次，21天或35天为一个周期。患者既往接受过中位3线（范围1-11线）治疗，50%的患者对PI难治。≥ 10%的患者报告的治疗相关3级或4级不良事件为血小板减少症（45%）、中性粒细胞减少症（24%）、疲乏（14%）和贫血（12%）。发病率（4例，10%）和等级（
Selinexor is an oral inhibitor of the nuclear export protein exportin 1. Preclinical studies demonstrated synergistic antimyeloma activity between selinexor and proteasome inhibitors (PI) through suppression of NF-kappa B signaling and nuclear retention of tumor suppressor proteins. We tested selinexor in combination with low-dose bortezomib and dexamethasone (SVd) for the treatment of relapsed or refractory multiple myeloma (MM). The primary objectives of this study were to determine the safety profile, overall response rate (ORR), and a recommended phase 2 dose (RP2D) of SVd. We enrolled 42 patients to receive selinexor (60, 80, or 100 mg orally) plus bortezomib (1.3 mg/m(2) subcutaneously) and dexamethasone (20 mg orally) once or twice weekly in 21- or 35-day cycles. Patients had a median of 3 (range 1-11) prior lines of therapy, and 50% were refractory to a PI. Treatment-related grade 3 or 4 adverse events reported in >= 10% of patients were thrombocytopenia (45%), neutropenia (24%), fatigue (14%), and anemia (12%). Incidence (4 patients, 10%) and grade (