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既往治疗对复发/难治性多发性骨髓瘤患者接受塞利尼索联合硼替佐米和地塞米松治疗结局的影响:BOSTON 试验的扩展随访亚组分析。

Impact of prior treatment on selinexor, bortezomib, dexamethasone outcomes in patients with relapsed/refractory multiple myeloma: Extended follow-up subgroup analysis of the BOSTON trial.

机构信息

Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Salamanca, Spain.

Interdisciplinary Cancer Center, University of Freiburg, Faculty of Freiburg, Freiburg, Germany.

出版信息

Eur J Haematol. 2024 Aug;113(2):242-252. doi: 10.1111/ejh.14223. Epub 2024 May 1.

Abstract

OBJECTIVES

To analyze the impact of prior therapies on outcomes with selinexor, bortezomib, and dexamethasone (SVd) versus bortezomib and dexamethasone (Vd) in 402 patients with relapsed/refractory multiple myeloma (RRMM) in the phase 3 BOSTON trial.

METHODS

Post hoc analysis of progression-free survival (PFS), overall survival (OS), and safety for lenalidomide-refractory, proteasome inhibitor (PI)-naïve, bortezomib-naïve, and one prior line of therapy (1LOT) patient subgroups.

RESULTS

At a median follow-up of over 28 months, clinically meaningful improvements in PFS were noted across all groups with SVd. The median SVd PFS was longer in all subgroups (lenalidomide-refractory: 10.2 vs. 7.1 months, PI-naïve: 29.5 vs. 9.7; bortezomib-naïve: 29.5 vs. 9.7; 1LOT: 21.0 vs. 10.7; p < .05). The lenalidomide-refractory subgroup had longer OS with SVd (26.7 vs. 18.6 months; HR 0.53; p = .015). In all subgroups, overall response and ≥very good partial response rates were higher with SVd. The manageable safety profile of SVd was similar to the overall patient population.

CONCLUSIONS

With over 2 years of follow-up, these clinically meaningful outcomes further support the use of SVd in patients who are lenalidomide-refractory, PI-naïve, bortezomib-naïve, or who received 1LOT (including a monoclonal antibody) and underscore the observed synergy between selinexor and bortezomib.

摘要

目的

在 3 期 BOSTON 试验中,分析 402 例复发/难治性多发性骨髓瘤(RRMM)患者中,先前接受过治疗对 selinexor、硼替佐米和地塞米松(SVd)与硼替佐米和地塞米松(Vd)治疗结局的影响。

方法

对 lenalidomide 耐药、蛋白酶体抑制剂(PI)初治、硼替佐米初治和一线治疗(1LOT)患者亚组的无进展生存期(PFS)、总生存期(OS)和安全性进行事后分析。

结果

在超过 28 个月的中位随访中,SVd 在所有组中均观察到 PFS 有显著改善。在所有亚组中,SVd 的中位 PFS 均更长(lenalidomide 耐药:10.2 与 7.1 个月,PI 初治:29.5 与 9.7 个月;硼替佐米初治:29.5 与 9.7 个月;1LOT:21.0 与 10.7 个月;均 P<.05)。SVd 在 lenalidomide 耐药亚组中 OS 更长(26.7 与 18.6 个月;HR 0.53;P=.015)。在所有亚组中,SVd 的总缓解率和≥非常好的部分缓解率更高。SVd 的安全性可管理,与总体患者人群相似。

结论

在超过 2 年的随访中,这些具有临床意义的结果进一步支持 SVd 在 lenalidomide 耐药、PI 初治、硼替佐米初治或接受过 1LOT(包括单克隆抗体)的患者中的应用,并强调了 selinexor 与硼替佐米之间的协同作用。

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