Selinexor in multiple myeloma

ABSTRACT

Introduction

Selinexor, an XPO1 inhibitor, has emerged as a promising therapeutic option in the challenging landscape of relapsed/refractory multiple myeloma (RRMM).

Areas covered

This article provides a review of selinexor, with a focus on available clinical studies involving MM patients and its safety profile. Clinical trials, such as STORM and BOSTON, have demonstrated its efficacy, particularly in combination regimens, showcasing notable overall response rates (ORR) and prolonged median progressionfree survival (mPFS). Selinexor’s versatility is evident across various combinations, including carfilzomibdexamethasone (XKd), lenalidomidedexamethasone (XRd), and pomalidomidedexamethasone (XPd), with efficacy observed even in tripleclass refractory and highrisk patient populations. However, challenges, including resistance mechanisms and adverse events, necessitate careful management. Realworld evidence also underscores selinexor’s effectiveness in RRMM, though dose adjustments and supportive measures remain crucial. Ongoing trials are exploring selinexor in diverse combinations and settings, including pomalidomidenaïve patients and postautologous stem cell transplant (ASCT) maintenance.

Expert opinion

The evolving landscape of selinexor’s role in the sequencing of treatment for RRMM, its potential in highrisk patients, including those with extramedullary disease, as revealed in the most recent international meetings, and ongoing investigations signal a dynamic era in myeloma therapeutics. Selinexor emerges as a pivotal component in multidrug strategies and innovative combinations.

KEYWORDS:

• Selinexor
• MM
• XPO1
• therapy

Article highlights

• Selinexor has emerged as a promising therapeutic option among the challenging landscape of relapsed/refractory multiple myeloma (RRMM).

• Operating by inhibiting the nuclear export function of XPO1, also known as Chromosome Region Maintenance 1, selinexor exerts its pharmacological effect.

• When utilized in conjunction with other anti-MM agents, XPO1 inhibitor demonstrates enhanced therapeutic effect.

• Promising applications of selinexor include its use as bridge therapy to CAR-T-cell therapy and as supplement to the conditioning regimen for ASCT.

• Ongoing studies extending the exploration of selinexor into NDMM patients, especially those with renal impairment (RI), highlight its potential in addressing specific clinical challenges.

• Real-world data provide complementary insights to those from clinical trials, providing valuable information on the effectiveness and tolerability of selinexor-based regimens in routine clinical practice for RRMM patients.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The present study is supported in part by Progetto Ricerca Finalizzata PNRR-MAD-2022-12375673 (Next Generation EU, M6/C2_CALL 2022), Italian Ministry of Health, Rome, Italy.