eligibility_summary
Adults >18 with high-risk SMM (≤40% BM PCs) per 20-2-20 (≥2 factors) or score ≥9, or ≥10% BM PCs plus evolving M-protein/Hb/FLC, abnormal immunophenotype with immunoparesis, or high-risk cytogenetics. No SLIM-CRAB/MDE. ECOG 0–1, adequate labs, CrCl ≥60, consent, contraception. Exclude prior SMM/active MM therapy, symptomatic MM, investigational/recent anti-MM/anti-BCMA tx, active infection, major comorbidity, CNS MM, recent cancer (exceptions), cardiac disease, recent surgery, pregnancy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Drugs/interventions and mechanisms: Ciltacabtagene autoleucel (cilta-cel) is an autologous, BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapy, engineered T cells bind BCMA on myeloma cells, activating T-cell cytotoxicity and cytokine release to eliminate malignant plasma cells. Cyclophosphamide is an alkylating agent (nitrogen mustard) used as lymphodepleting chemotherapy, DNA crosslinking reduces host lymphocytes to promote CAR-T expansion. Fludarabine (phosphate) is a purine nucleoside analog, lymphodepleting chemotherapy that inhibits DNA synthesis and depletes lymphocytes. Cells/pathways targeted: BCMA (TNFRSF17)-expressing clonal plasma cells in high-risk smoldering multiple myeloma, effector pathway is CAR-mediated T-cell activation, preconditioning targets host lymphocytes (including regulatory T cells) to enhance CAR-T engraftment/persistence.