Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Salamanca, Spain.
Interdisciplinary Cancer Center, University of Freiburg, Faculty of Freiburg, Freiburg, Germany.
Eur J Haematol. 2024 Aug;113(2):242-252. doi: 10.1111/ejh.14223. Epub 2024 May 1.
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.
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.
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.
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.
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。
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。
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。
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。