每周一次塞来昔布、卡非佐米和地塞米松治疗卡非佐米难治性多发性骨髓瘤患者。
Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients.
机构信息
Duke University Medical Center, Durham, NC, USA.
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
出版信息
Br J Cancer. 2022 Mar;126(5):718-725. doi: 10.1038/s41416-021-01608-2. Epub 2021 Nov 20.
BACKGROUND
Proteasome inhibitors (PIs), including carfilzomib, potentiate the activity of selinexor, a novel, first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in preclinical models of multiple myeloma (MM).
METHODS
The safety, efficacy, maximum-tolerated dose (MTD) and recommended phase 2 dose (RP2D) of selinexor (80 or 100 mg) + carfilzomib (56 or 70 mg/m) + dexamethasone (40 mg) (XKd) once weekly (QW) was evaluated in patients with relapsed refractory MM (RRMM) not refractory to carfilzomib.
RESULTS
Thirty-two patients, median prior therapies 4 (range, 1-8), were enrolled. MM was triple-class refractory in 38% of patients and 53% of patients had high-risk cytogenetics del(17p), t(4;14), t(14;16) and/or gain 1q. Common treatment-related adverse events (all/Grade 3) were thrombocytopenia 72%/47% (G3 and G4), nausea 72%/6%, anaemia 53%/19% and fatigue 53%/9%, all expected and manageable with supportive care and dose modifications. MTD and RP2D were identified as selinexor 80 mg, carfilzomib 56 mg/m, and dexamethasone 40 mg, all QW. The overall response rate was 78% including 14 (44%) ≥ very good partial responses. Median progression-free survival was 15 months.
CONCLUSIONS
Weekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM.
背景
蛋白酶体抑制剂（PIs），包括卡非佐米，可增强新型、首创的核输出（SINE）化合物选择性抑制剂塞利尼索与多发性骨髓瘤（MM）的临床前模型中的活性。
方法
评估了塞利尼索（80 或 100mg）+卡非佐米（56 或 70mg/m）+地塞米松（40mg）（XKd）每周一次（QW）联合治疗复发难治性多发性骨髓瘤（RRMM）且对卡非佐米不耐药患者的安全性、疗效、最大耐受剂量（MTD）和推荐的 II 期剂量（RP2D）。
结果
32 例患者，中位既往治疗线数为 4（范围 1-8），纳入研究。38%的患者为三药难治性，53%的患者存在高危细胞遗传学 del(17p)、t(4;14)、t(14;16)和/或获得 1q。常见的治疗相关不良事件（全部/3 级）为血小板减少症 72%/47%（G3 和 G4）、恶心 72%/6%、贫血 53%/19%和疲劳 53%/9%，所有不良事件均通过支持性护理和剂量调整可管理。确定了塞利尼索 80mg、卡非佐米 56mg/m 和地塞米松 40mg，所有 QW 的 MTD 和 RP2D。总缓解率为 78%，包括 14 例（44%）≥非常好的部分缓解。中位无进展生存期为 15 个月。
结论
每周 XKd 非常有效且耐受良好。这些数据支持进一步研究 XKd 在多发性骨髓瘤患者中的应用。
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