OC.57 Safety and efficacy of CD19 NEX-T® (BMS-986353), a chimeric antigen receptor (CAR) T cell therapy, in systemic sclerosis (SSc): findings from the breakfree-1 trial
Year: 2026
Type: conference-paper
Abstract: 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.
Authors: Dinesh Khanna, David S Korman, Vikas Majithia, Elana J Bernstein, Philip Mease, Melissa Griffith, Maria F Carpintero, Mark H Wener, David Simon, Neil Kramer, Georg Schett, Ignacio Gómez-García, Maureen D Mayes, Alisha Desai, Alexis Melton, Whitney Handy, San-San Ou, Praneeth Jarugula, Takafumi Ide, Melissa Harnois, Jerill Thorpe, Ashley Koegel, Margrit Wiesendanger
Institutions: University of Michigan, HealthONE, Mayo Clinic in Florida, Columbia University Irving Medical Center, University of Washington, Swedish Medical Center, University of Colorado Anschutz, University of Miami, University of Washington Medical Center, Charité – Universitätsmedizin Berlin, Overlook Medical Center, Atlantic Health System, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Hospital Universitario Reina Sofía, The University of Texas Health Science Center at Houston, Bristol-Myers Squibb (United States), Icahn School of Medicine at Mount Sinai
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W7163645301