As a selective inhibitor of nuclear export (XPO1), XPOVIO blocks the transport of tumor suppressor proteins out of the nucleus, restoring their activity and driving cancer cell apoptosis. It is approved for relapsed/refractory multiple myeloma and relapsed/refractory DLBCL after at least two prior systemic therapies, thereby expanding treatment options in these hard-to-treat malignancies. If further evaluated and approved in acute lymphoblastic leukemia (ALL), it could significantly expand the eligible patient population by providing a novel targeted option for relapsed/refractory ALL, addressing a high unmet need and broadening the overall therapeutic landscape.

Preclinical and Phase II evidence indicates that XPOVIO may improve outcomes in AML by enhancing sensitivity to cytarabine and anthracycline-based chemotherapy, supporting its potential as a chemosensitizing agent in acute leukemias.

Efficacy results:

• Median Overall Survival (OS): 991 days with selinexor plus standard chemotherapy vs 649 days with standard chemotherapy alone.
• Response Rate: 77% (33/43) in the selinexor arm vs. 50% (7/14) in the control arm.
• Risk Ratio for Response: 1.53 (95% CI, 1.01–4.57).
• Although the response rate favored the selinexor arm, the difference did not reach statistical significance (p = 0.09).
• The study was terminated early, limiting its statistical power to detect significant survival differences.

Safety results:

• 30-day mortality: 11.6% (5/43) in the selinexor arm vs. 14.3% (2/14) in the control arm.
• Seven (16%) patients in the selinexor group had prolonged thrombocytopenia. 
• Diarrhea and nausea were, furthermore, the most commonly observed adverse events with selinexor.
• The addition of selinexor to intensive induction and consolidation chemotherapy was feasible.
• No unexpected safety signals were observed.

KOL insights

“Although the response and survival rates were numerically higher with selinexor, these findings were not statistically significant.” –Expert Opinion

“Selinexor may enhance the efficacy of standard chemotherapy in AML, demonstrating higher response rates and longer overall survival without new safety concerns.” Expert Opinion

Conclusion

Acute myeloid leukemia (AML) remains a growing global health burden, driven by population ageing, improved diagnostic capabilities, and enhanced cancer surveillance. Despite advances in diagnosis and treatment, significant regional disparities persist, with higher-income countries achieving better survival outcomes than resource-limited settings.

The AML treatment landscape has evolved significantly in recent years with the introduction of molecularly targeted therapies, including REVUFORJ for KMT2A-rearranged leukemia, REZLIDHIA for IDH1-mutated AML, and XOSPATA for FLT3-mutated disease. Despite these advances, many patients, particularly those with intermediate and poor-risk AML continue to experience relapse and suboptimal long-term outcomes, highlighting the need for novel therapeutic approaches beyond mutation-specific targeting.

Against this competitive backdrop, selinexor offers a differentiated mechanism through inhibition of nuclear export, with the potential to enhance the efficacy of conventional chemotherapy across broader patient populations. While competition from established targeted therapies and emerging combination regimens remains intense, selinexor's biomarker-agnostic approach could provide a complementary treatment strategy.