eligibility_summary
Eligible: newly diagnosed multiple myeloma with high‑risk cytogenetics, may have had 1 urgent bortezomib‑based cycle. ECOG≤2, ANC≥1K (≥500 if >50% marrow PCs), platelets≥100K (≥50K), bilirubin≤1.5×ULN, AST/ALT≤3×ULN, GFR≥30. Controlled HIV/HBV/HCV allowed, treated CNS OK, NYHA≤2B, non‑interfering malignancies allowed, contraception and lenalidomide REMS required, consent. Exclude: unresolved >G1 AEs, other trials, selinexor allergy, strong CYP3A4 modulators, uncontrolled illness, pregnancy/breastfeeding.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 2 randomized trial in high-risk newly diagnosed multiple myeloma comparing Dara-SVD (daratumumab+rHuPH20, selinexor, bortezomib, dexamethasone) vs Dara-RVD (daratumumab+rHuPH20, lenalidomide, bortezomib, dexamethasone). Drugs/mechanisms: selinexor—oral small-molecule SINE, inhibits XPO1/CRM1 nuclear export, retains tumor suppressors, induces myeloma apoptosis, daratumumab—anti-CD38 IgG1 mAb (SC with hyaluronidase for absorption), mediates CDC, ADCC/ADCP, depletes CD38+ plasma cells, bortezomib—reversible 26S proteasome inhibitor (boronic acid), disrupts UPR and NF-κB, kills plasma cells, lenalidomide—oral IMiD, binds cereblon, degrades IKZF1/3, boosts T/NK cells, dexamethasone—glucocorticoid, pro-apoptotic and anti-inflammatory. Targets/pathways: malignant plasma cells, CD38, XPO1, ubiquitin–proteasome/NF-κB, CRBN–IKZF1/3, immune effector ADCC/ADCP.