Selinexor + Ruxolitinib combination

Current understanding

To be populated as evidence accumulates.

Evidence log

• 2026-06-02 — Selinexor Plus Ruxolitinib in Janus Kinase Inhibitor-Naïve Myelofibrosis: Phase III SENTRY Trial.: Phase III SENTRY (trial-late) full readout in JAKi-naïve MF: selinexor + ruxolitinib significantly improved SVR35 at week 24 vs ruxolitinib alone but did not improve AbsTSS; early overall-survival signal observed with expected additive hematologic toxicity. (novelty: 3)
• 2026-07-01 — Selinexor in combination with azacitidine or ruxolitinib in myelodysplastic/myeloproliferative neoplasm overlap syndromes: A multicenter prospective study.: Multicenter prospective study (trial-early) of selinexor + ruxolitinib (or + azacitidine) specifically in MDS/MPN overlap syndromes reports 60% ORR with manageable safety — extends the selinexor+ruxolitinib program beyond MF into the MDS/MPN overlap setting. (novelty: 3)
• 2026-07-14 — Targeting nuclear export and Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signalling in myelofibrosis: A novel combinatorial strategy that impacts intrinsic and microenvironment-related pathways.: Preclinical multi-omic study shows selinexor + ruxolitinib more potently suppresses MF progenitor fitness than JAK2 inhibition alone by restoring nuclear tumor suppressors and disrupting JAK/STAT plus NF-κB-driven inflammatory signaling in both malignant cells and the microenvironment, with activity retained in ruxolitinib-resistant models. (novelty: 3)
• 2026-07-02 — A Study to Evaluate Single Agent Selinexor Versus Physician’s Choice in Participants With Previously Treated Myelofibrosis: Trial-early: Randomized Phase 2 of selinexor monotherapy vs physician’s choice in JAKi-pretreated MF complements the SENTRY combination program by testing XPO1 inhibition as salvage rather than add-on, informing sequencing decisions relative to selinexor+ruxolitinib upfront use. (novelty: 3)
• 2026-06-08 — Selinexor in Myelofibrosis Refractory or Intolerant to JAK1/2 Inhibitors: Trial-early: Phase II single-arm trial of selinexor monotherapy in JAKi-refractory/intolerant MF extends the XPO1-inhibitor program into the post-ruxolitinib salvage setting, complementing the combination (SENTRY), JAKi-naïve monotherapy, and pacritinib-combination contexts. (novelty: 3)
• 2026-06-04 — Selinexor Monotherapy for Cytoreduction in BCR::ABL1-Negative Myeloproliferative Neoplasms: Trial-early: Phase 2 single-arm trial of selinexor monotherapy as cytoreduction across PV/ET/PMF further broadens the XPO1-inhibitor program beyond the ruxolitinib-combination (SENTRY) and JAKi-naïve MF monotherapy contexts. (novelty: 4)
• May 21, 20 — CALR Mutation–Directed Agents and Targeted Therapies Represent Key Research Avenue in MPN Management: Review-level synthesis (May 2026) reiterates SENTRY Phase 3 first co-primary endpoint (spleen volume reduction) was met, positioning selinexor+ruxolitinib alongside MANIFEST-3 (pelabresib), IMpactMF (imetelstat), and CALR-directed INCA033989 as key emerging frontline/combination MF strategies. (novelty: 3)
• May 12, 20 — CALR Mutation–Directed Agents and Targeted Therapies Represent Key Research Avenue in MPN Management: Review-level synthesis: positions SENTRY selinexor+ruxolitinib readout alongside pelabresib and imetelstat as key emerging MPN trial data within a broader precision-medicine landscape targeting JAK2/CALR/MPL drivers. (novelty: 3)
• 2026-02-12 — A Study of Selinexor Monotherapy in Subjects With JAK Inhibitor-naïve Myelofibrosis and Moderate Thrombocytopenia: Trial-early: parallel investigation of selinexor as monotherapy (not combination) in JAKi-naïve MF with moderate thrombocytopenia broadens the XPO1-inhibitor program beyond the ruxolitinib-combination context. (novelty: 3)
• 2026-04-09 — Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis: Trial-late: Global Phase 1/3 trial registered evaluating selinexor + ruxolitinib vs placebo + ruxolitinib in JAK inhibitor-naïve myelofibrosis (consistent with SENTRY program design). (novelty: 3)
• 2026-03-18 — Selinexor and Pacritinib in JAK Inhibitor-naïve MF Patients With Cytopenias: cross-connection with selinexor-pacritinib-combination: Both combinations pair the XPO1 inhibitor selinexor with a JAK inhibitor backbone; the pacritinib pairing extends the strategy specifically to cytopenic, JAKi-naïve MF where ruxolitinib dosing is constrained. (novelty: 4)
• 2026-03-24 — Karyopharm Phase 3 SENTRY Trial in Myelofibrosis Met First Co-Primary Endpoint: Phase 3 SENTRY trial (trial-late) met first co-primary endpoint of spleen volume reduction vs ruxolitinib alone; 32% vs 24% achieved ≥20% VAF reduction across JAK2/MPL/CALR; symptom burden (Abs-TSS) co-primary endpoint not met. (novelty: 4)

Open questions

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