The expanding therapeutic options for relapsed/refractory multiple myeloma (RRMM) have created new opportunities for strategic treatment sequencing, yet managing disease progression as response durability declines remains a persistent challenge.1 Selective inhibitors of nuclear export (SINEs) that target exportin 1 (XPO1) offer a mechanistically novel approach, providing meaningful disease control and bridging options for patients progressing after standard classes or awaiting cellular immunotherapy.2 The mechanistic independence from immune modulation makes them particularly valuable for patients ineligible for immune-based therapies.
SINE agents demonstrate a favorable tolerability profile characterized by manageable hematologic and gastrointestinal adverse events without cumulative neurotoxicity or profound immunosuppression.3,4 Their oral administration facilitates outpatient management and supports maintenance of quality of life, an increasingly important factor as patients move through multiple lines of therapy.3 This aligns with patient-reported treatment priorities, which emphasize minimizing adverse events, maintaining convenience, and reducing treatment burden, particularly in community settings where most RRMM care is delivered.5,6
For patients with high-risk cytogenetics, including del(17p) or t(4;14), SINEs offer meaningful clinical benefit through their unique mechanism independent of immune function.7 This strategy supports disease management in patients unable to receive immune-based therapies or specialized interventions like stem cell transplant are limited due to medical contraindications, access barriers, or patient preferences.6
Strategic deployment of SINEs for RRMM proves especially valuable for patients managing disease in community settings. For patients who are not candidates for cellular therapies, these agents offer disease control with a practical administration schedule that considers both efficacy and patient-centered factors, such as reduced treatment burden, flexible outpatient use, and manageable adverse events.4 Additionally, the non-overlapping safety profile allows sequential use with limited effect on patient performance status or treatment eligibility.
Clinical evidence supports integrating SINEs at multiple treatment points, whether in earlier relapse to preserve eligibility for future options, during holding periods before definitive therapies, or in later lines for heavily pretreated patients.1,7 These agents provide a treatment option that is accessible in both academic and community settings, helping reduce disparities in care delivery and supporting continuity of therapy across diverse healthcare environments.6
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