Department of Clinical Therapeutics, Plasma Cell Dyscrasia Unit, National and Kapodistrian University of Athens, School of Medicine, Greece.
Department of Clinical Therapeutics, Plasma Cell Dyscrasia Unit, National and Kapodistrian University of Athens, School of Medicine, Greece.
Clin Lymphoma Myeloma Leuk. 2023 Nov;23(11):844-849. doi: 10.1016/j.clml.2023.07.013. Epub 2023 Aug 1.
Selinexor is an orally available selective inhibitor of exportin-1 that has offered a new treatment option in relapsed or refractory myeloma (RRMM) either in combination with dexamethasone (Sd) or with bortezomib and dexamethasone (SVd).
PATIENTS-METHODS: We evaluated the efficacy and toxicity of selinexor combinations in the real world, post progression therapies and their outcomes. The analysis included 44 patients with RRMM treated with Sd (N = 21, 48%) or SVd (N = 23, 52%).
On intent-to-treat, response rate (ORR) among all treated patients was 29.5% (13/44, of which CR: 2, VGPR: 3, PR:8); ORR was 35% for SVd and 24% for Sd. Median PFS was 3.0 months for all; 6.9 months for responders (≥PR),2.7 months for Sd and 3.4 months for SVd treated patients. In univariate analysis, serum albumin <3.5 g/dl and LDH >ULN were associated with worse PFS (P = .001 and P = .032, respectively).The OS of the whole cohort exceeded one year while serum albumin <3.5 gr/dl and LDH>ULN were associated with worse OS. After progression to Sd/SVd, 20 patients received further therapy; on ITT, the ORR was 40% (8/20) and the subsequent PFS was 3.4 months. The most common adverse events were fatigue, thrombocytopenia and nausea, while the most recorded grade 3 or 4 side effect was thrombocytopenia; 56% (25/44) of patients required dose reduction, however, this was not associated with inferior PFS.
In conclusion, selinexor-based therapy provides an additional treatment option in the real word setting and with appropriate dosing and toxicity management a subset of patients may have significant benefit.
Selinexor 是一种口服型选择性核输出蛋白 1 抑制剂，为复发或难治性多发性骨髓瘤（RRMM）提供了一种新的治疗选择，可与地塞米松（Sd）联合使用，也可与硼替佐米和地塞米松（SVd）联合使用。
我们评估了 Selinexor 联合治疗在真实世界、后线治疗中的疗效和毒性及其结局。该分析纳入了 44 例接受 Sd（N=21，48%）或 SVd（N=23，52%）治疗的 RRMM 患者。
意向治疗人群中，所有治疗患者的缓解率（ORR）为 29.5%（44 例患者中有 13 例，其中完全缓解[CR]2 例，非常好的部分缓解[VGPR]3 例，部分缓解[PR]8 例）；SVd 组的 ORR 为 35%，Sd 组为 24%。所有患者的中位无进展生存期（PFS）为 3.0 个月；缓解者（≥PR）的中位 PFS 为 6.9 个月，Sd 组为 2.7 个月，SVd 组为 3.4 个月。单因素分析显示，血清白蛋白<3.5 g/dl 和乳酸脱氢酶（LDH）>正常值上限（ULN）与较差的 PFS 相关（P=0.001 和 P=0.032）。全队列的总生存期（OS）超过 1 年，而血清白蛋白<3.5 g/dl 和 LDH>ULN 与较差的 OS 相关。在进展至 Sd/SVd 后，20 例患者接受了进一步治疗；在意向治疗人群中，ORR 为 40%（8/20），随后的 PFS 为 3.4 个月。最常见的不良反应是疲劳、血小板减少和恶心，而最常见的 3 级或 4 级不良反应是血小板减少症；44 例患者中有 56%（25 例）需要减少剂量，但这与较差的 PFS 无关。
总之，Selinexor 为基础的治疗方案在真实世界中提供了另一种治疗选择，通过适当的剂量和毒性管理，一部分患者可能会获得显著的获益。
