Purpose: Selinexor is an oral selective inhibitor of exportine-1 (XPO1) with efficacy as a single agent in heavily pretreated diffuse large B-cell lymphoma (DLBCL). We conducted a study investigating the combination of selinexor with rituximab and platinum-based chemotherapy in B-cell lymphoma. Patients and methods: We conducted a phase 1b, dose-escalation, and expansion trial, which enrolled patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Patients received oral selinexor according to a 3 + 3 design in combination with rituximab and dexamethasone, high-dose cytarabine, oxaliplatine (DHAOX) or gemcitabine, dexamethasone, and cisplatin (GDP) chemotherapy. Results: A total of 39 patients were enrolled, 27 during the escalation phase and 12 during the expansion phase. Most patients had diffuse large B-cell lymphoma (DLBCL; 77%). Group R-DHAOX was prematurely closed to inclusion due to a recommendation from the French drug agency, independent of this trial. A recommended phase 2 dose (RP2D) of selinexor in association with R-GPD was established at 40 mg on days 1, 8, and 15 of each 21-day cycle. In a population of 18 patients treated at this dose of selinexor, the most frequent grade 3–4 adverse events were hematological. With this regimen, seven obtained a complete metabolic response and five a partial response. The median PFS was 5.8 months. Conclusions: Among the patients with R/R B-cell lymphoma, selinexor at a weekly dose of 40 mg with R-GDP is feasible for outpatients, with a generally acceptable safety profile.
目的：Selinexor是一种口服的选择性核输出蛋白-1（XPO1）抑制剂，在经深度预处理的弥漫性大B细胞淋巴瘤（DLBCL）患者中作为单药显示出疗效。本研究旨在探讨selinexor联合利妥昔单抗及铂类化疗方案在B细胞淋巴瘤中的治疗效果。患者与方法：我们开展了一项Ib期剂量递增及扩展试验，入组了复发或难治性B细胞非霍奇金淋巴瘤患者。患者根据3+3设计口服selinexor，联合利妥昔单抗及地塞米松、大剂量阿糖胞苷、奥沙利铂（DHAOX）或吉西他滨、地塞米松、顺铂（GDP）化疗方案。结果：共入组39例患者，其中27例处于剂量递增阶段，12例处于扩展阶段。大多数患者为弥漫性大B细胞淋巴瘤（DLBCL；77%）。R-DHAOX组因法国药品监管机构的建议（独立于本试验）提前终止入组。确定了selinexor联合R-GDP方案的推荐II期剂量（RP2D）为每21天周期的第1、8、15天口服40 mg。在18例接受该剂量selinexor治疗的患者中，最常见的3-4级不良事件为血液学毒性。采用该方案后，7例患者获得完全代谢缓解，5例获得部分缓解。中位无进展生存期（PFS）为5.8个月。结论：在复发/难治性B细胞淋巴瘤患者中，每周40 mg剂量的selinexor联合R-GDP方案对门诊患者可行，且安全性总体可接受。
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