Selinexor plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis: a multicenter, open-label, phase 1 study
Clinical Snapshot
PICO Framework
| P — Population | JAK inhibitor-naïve patients with myelofibrosis (n=24) |
| I — Intervention | Selinexor (40mg or 60mg once weekly) plus ruxolitinib |
| C — Comparator | Dose comparison between 40mg and 60mg selinexor groups |
| O — Outcomes | Maximum tolerated dose, safety, spleen volume reduction ≥35% (SVR35), total symptom score reduction ≥50% (TSS50) |
Bottom Line
This phase 1 study suggests selinexor 60mg weekly combined with ruxolitinib may offer superior spleen and symptom responses compared to lower doses in JAK inhibitor-naïve myelofibrosis patients. The combination appeared tolerable with manageable toxicities, though the small sample size (n=24) and non-randomised design limit definitive conclusions. The 79% spleen volume reduction rate in the 60mg group is encouraging, particularly given that 100% of patients receiving suboptimal ruxolitinib doses still achieved spleen responses. However, four deaths occurred during the study, highlighting the need for careful patient selection and monitoring. While these preliminary results support progression to phase 3 trials, clinicians should await larger randomised studies before considering this combination as standard care. The findings are relevant to Australian practice given PBS access to ruxolitinib, though selinexor availability would require regulatory approval.
Key Findings
P Value: Not reported
Effect Size: SVR35: 79% (60mg group) vs 38% (40mg group); TSS50: 58% vs 25%
Primary Outcome: Maximum tolerated dose: 60mg selinexor weekly with ruxolitinib
Nnt Or Sensitivity: Number needed to treat approximately 2.4 for additional SVR35 response with 60mg vs 40mg dose
Confidence Interval: Not reported
Clinical Application
Requires specialist haematology centres with experience in exportin-1 inhibitors and supportive care protocols Ruxolitinib is PBS-listed for myelofibrosis; selinexor would require special access scheme or future TGA approval for this indication JAK inhibitor-naïve myelofibrosis patients suitable for combination therapy
Abstract
The phase 1 portion of SENTRY/XPORT-MF-034 (NCT04562389) evaluated the exportin 1 inhibitor selinexor (40 mg/60 mg once weekly) plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis (n = 24). Primary end points were maximum tolerated selinexor dose, recommended clinical trial dose, and safety. No dose-limiting toxicities were reported. Common adverse events were nausea, fatigue, anemia, thrombocytopenia, constipation, vomiting, and headache. Nausea was transient, mainly grade 1, and managed by prophylactic antiemetics. Four deaths occurred, all unrelated to study treatment. Selinexor 60 mg in combination with ruxolitinib was identified as the recommended phase 3 dose based on safety, efficacy, and exposure-response analyses. Overall safety profiles and grades of clinically significant adverse events were similar and generally manageable regardless of selinexor dose. A greater proportion of patients achieved spleen volume reduction of ≥35% (SVR35) and total symptom score reduction of ≥50% (TSS50) at week 24 in the selinexor 60-mg group (79% and 58%) than the 40-mg group (38% and 25%). Among evaluable patients who received suboptimal ruxolitinib ≤5 mg twice daily in the selinexor 60-mg group, SVR35 was observed in 100% (6/6) and TSS50 in 75% (3/4) of patients. The trial was registered at ClinicalTrials.gov as NCT04562389.
References
- 1.Ali, H., Mohan, S., Kishtagari, A., Prchal, J. T., Maher, K., Chai, Y., Gudi, G., Taverna, P., Mark, T., & Tantravahi, S. K. (2026). Selinexor plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis: a multicenter, open-label, phase 1 study. Blood Advances. https://doi.org/10.1182/bloodadvances.2025018706
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