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Single-Agent Selinexor Versus Physician's Choice in Previously Treated Myelofibrosis: Results From the Phase 2
Sebastian Grosicki1, Habte Yimer2, Rosa Ayala3
1Department of Cancer Prevention Medical University of Silesia Katowice Poland.
Background:
Janus kinase inhibitors (JAKis), the current standard of care for myelofibrosis (MF), provide clinical benefit, but responses are frequently incomplete, non-durable, and associated with cytopenias, underscoring the need for therapies with novel mechanisms of action. Selinexor, an oral selective inhibitor of Exportin 1 (XPO1), modulates nuclear-cytoplasmic transport, inflammatory signaling, and cancer cell proliferation.
Methods:
XPORT-MF-035, a global, Phase 2, randomized, open-label study comparing selinexor monotherapy with physician's choice (PC) in MF previously treated with JAKi, randomized patients 1:1 to selinexor or PC, with crossover permitted upon disease progression or inadequate spleen response. Primary endpoint was spleen volume reduction ≥ 35% (SVR35). Additional endpoints included symptom improvement, hematologic outcomes, plasma cytokine analyses, and safety.
Results:
Twenty-four patients were enrolled and treated. In the efficacy-evaluable population, SVR35 at any time was achieved by 29% (2/7) and 13% (1/8) of selinexor- and PC-treated patients, respectively; 8% (1/12) in each arm achieved SVR35 at Week 24 in the intent-to-treat population. Among evaluable patients, 40% (2/5) achieved SVR35 following selinexor crossover. Symptom improvement was observed with selinexor but not PC. Selinexor-treated patients experienced fewer Grade ≥ 3 anemia events with lower transfusion burden and reductions in multiple proinflammatory cytokines. Selinexor was generally well tolerated; common treatment-emergent adverse events (TEAEs) included anemia, asthenia, and decreased weight. One TEAE leading to death occurred in the selinexor and two in PC; none were considered treatment-related.
Conclusions:
Despite limited sample size, XPORT-MF-035 provides descriptive data on the safety, tolerability, and biological activity of selinexor monotherapy in previously treated MF, supporting further evaluation in this population.
Trial Registration:
ClinicalTrials.gov identifier: NCT04562870.
Insights
Selinexor shows promise in myelofibrosis patients previously treated with JAK inhibitors, demonstrating symptom improvement and favorable safety profiles. Further research is warranted for this novel therapy.
Area of Science:
- Oncology
- Hematology
- Pharmacology
Background:
- Janus kinase inhibitors (JAKis) are standard for myelofibrosis (MF) but have limitations.
- Novel therapies are needed due to incomplete and non-durable responses to JAKis.
- Selinexor, an oral Exportin 1 (XPO1) inhibitor, offers a new mechanism of action.
Purpose of the Study:
- To evaluate selinexor monotherapy versus physician's choice (PC) in MF patients previously treated with JAKi.
- To assess spleen volume reduction (SVR35) and symptom improvement.
- To analyze hematologic outcomes, cytokine profiles, and safety.
Main Methods:
- Phase 2, randomized, open-label study (XPORT-MF-035) comparing selinexor and PC.
- 1:1 randomization with crossover permitted.
- Primary endpoint: SVR35; secondary endpoints: symptoms, hematologic data, cytokines, safety.
Main Results:
- SVR35 at any time was achieved by 29% of selinexor-treated and 13% of PC-treated patients (evaluable population).
- Selinexor demonstrated symptom improvement, unlike PC.
- Selinexor showed fewer Grade ≥3 anemia events and reduced pro-inflammatory cytokines, with generally good tolerability.
Conclusions:
- Selinexor monotherapy shows potential in previously treated MF patients.
- The study provides descriptive data on selinexor's safety, tolerability, and biological activity.
- Further investigation of selinexor in this patient population is supported.
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