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Introduction In severe refractory SSc, treatments that halt disease progression and improve long-term outcomes are needed. BMS-986353, a CD19-directed CAR T NEX-T cell therapy, showed early efficacy and manageable safety in severe refractory autoimmune diseases in the Breakfree-1 trial ( NCT05869955). We present updated SSc cohort data.Material and Methods This phase 1 study enrolled patients with severe refractory SSc, including recently progressive diffuse cutaneous SSc (dcSSc) or SSc-related interstitial lung disease (ILD) with inadequate response to >/=1 immunosuppressive therapy (IST). Patients received a single BMS-986353 infusion of 10×10^6 (n=15) or 25×10^6 (n=1) CAR T cells after lymphodepletion (LD); SSc-directed therapies were discontinued before LD. Primary endpoint: safety.Results As of July 4, 2025, 16 patients received BMS-986353. Median follow-up was 139.5 (range, 10–383) days. Before enrollment, patients had received a median of 2.5 (1–6) ISTs. Median (range) modified Rodnan skin score (mRSS) at baseline was 26.5 (4–48). All patients were safety evaluable; 9 were efficacy evaluable (7 with SSc-ILD evaluable for pulmonary response; 9 patients with cutaneous disease evaluation [6 dcSSc, 3 limited cutaneous SSc]).All inflammatory adverse events (AEs) were reversible and most were low grade (Gr). Cytokine release syndrome occurred in 9 patients (7 Gr1, 2 Gr2) with median duration of 2 days. Five patients developed immune effector cell-associated neurotoxicity syndrome (3 Gr1, 1 Gr2, 1 Gr3), resolving in median of 3 days. Two patients had reversible Gr>/=3 hematologic treatment-emergent AEs (neutropenia, n=2; leukopenia, n=2).Median reduction in mRSS from baseline in patients with dcSSc was 10.0 points at month 3 (n=6); 13.0 points at month 9 (n=3; figure 1). Median absolute increase in percent of predicted forced vital capacity in patients with ILD was 3.0% at month 3 (n=7); 5.0% at month 6 (n=4). Four of 5 patients with >/=6 months follow-up achieved revised Composite Response Index in Systemic Sclerosis-25 by month 6. Eleven of 12 patients with >/=1 month of follow-up remained off SSc-specific IST; 1 patient with low pulmonary reserve at baseline and no clinical worsening received nintedanib. Robust CAR T cell expansion and complete peripheral B-cell depletion was achieved in all patients; lymph node biopsy from 1 patient at baseline and 3 weeks post-infusion showed complete B-cell depletion based on single-cell RNA sequencing (figure 2). SSc-related autoantibodies decreased post-BMS-986353 infusion.Conclusions BMS-986353 demonstrated a manageable safety profile and meaningful clinical improvement in patients with severe refractory SSc who remained off IST at follow-up.Abstract OC.57 Figure 1(A) mRSS in evaluable patients with SSc and (B) FVC in patients with SSc-ILD ≥ 1 montha post-BMS-986353Abstract OC.57 Figure 2(A) UMAP plot showing different cells and (B) proportion of each cell type pre- and post-infusion in lymph-node biopsy from 1 patient in the phase 1 trial