MINI REVIEW article
Front. Oncol.
Sec. Hematologic Malignancies
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1649493
Lower dose and weekly schedules of selinexor in multiple myeloma - updated evidence on safety and efficacy
Provisionally accepted
- 1Vanderbilt University Medical Center, Nashville, United States
- 2University of California Los Angeles David Geffen School of Medicine, Los Angeles, United States
- 3Karyopharm Therapeutics Inc, Newton, United States
- 4Duke University Medical Center, Durham, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Selinexor, a first-in-class, oral exportin-1 inhibitor, showed activity in penta-refractory multiple myeloma (MM) in early trial exploration; however, the side-effect profile of twice-weekly dosing led to hesitant incorporation into widespread practice. Here, our objective is to provide updated clinical evidence highlighting the preserved efficacy and improved tolerability of once-weekly selinexor at lower doses in patients with previously treated MM compared to twice-weekly regimens. Methods: Patient-level data from the BOSTON, STOMP, STORM, and XPORT-MM-028 clinical trials were systematically evaluated to elucidate relationships between selinexor dosing schedule, regimen toxicities, and efficacy in patients with MM that had progressed after at least one prior therapy. Results: Updated results on once-weekly selinexor in combination with other anti-MM agents showed a reduced adverse event profile and improved tolerability compared with twice-weekly selinexor regimens, without compromise in efficacy. Furthermore, new data from several regimens with weekly selinexor delivery suggest that patients who had selinexor dose reductions or were treated in cohorts with a lower selinexor starting dose had reduced rates of adverse events, and superior durations of response. Weekly selinexor in combination with pomalidomide or carfilzomib in particular showed efficacy in difficult-to-treat, multiclass relapsed/refractory MM, including MM refractory to prior BCMA-directed therapies. Conclusions: In a rapidly evolving field of previously treated MM, lowering of selinexor dose and frequency into weekly regimens showed a more feasible and tolerable treatment with continued efficacy when compared to twice-weekly schedules, paving the path for effective management of multiclass refractory MM, including patients with very advanced disease.
Keywords: Selinexor, Multiple Myeloma, Drug administration schedules, exportin 1, Antagonists and, inhibitors, combination drug therapy, clinical efficacy
Received: 18 Jun 2025; Accepted: 22 Aug 2025.
Copyright: © 2025 Baljevic, Schiller, Mark, Van Domelen and Gasparetto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Muhamed Baljevic, Vanderbilt University Medical Center, Nashville, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.