{
  "abstract": "Objectives In Breakfree-1 ( NCT05869955), BMS-986353 (CD19 NEX-T®), a CD19-directed CAR T cell therapy, showed promising early safety and efficacy in severe, refractory SLE. We report updated data for SLE cohort.Methods Breakfree-1 enrolled patients with active, severe (recent BILAG A score) SLE, with inadequate response to at least 2 immunosuppressants and steroids. Following lymphodepletion, a single BMS-986353 infusion was administered at 10×10^6 (dose level [DL] 1) or 25×10^6 CAR+ T cells (DL2). SLE-directed therapies were discontinued before lymphodepletion. Primary endpoint: safety.Results As of August 14, 2025, 26 patients were treated with DL1 and 6 with DL2. Patients were highly refractory with a median of 7 (range, 3–13) prior therapies. Median baseline SLEDAI-2K score was 12.0 (range, 2.0–30.0); median follow-up was 19.4 (range, 2.6–91.1) weeks at DL1.Dose-limiting toxicities occurred at a lower incidence in DL1 (8.0%) compared with DL2 (33.3%). DL1 was selected as the recommended phase 2 dose (RP2D) based on Bayesian optimal interval design and the cumulative pharmacokinetic, pharmacodynamic, and preliminary clinical data. Most TEAEs related to BMS-986353 occurred within 90 days post-infusion at RP2D. The most frequent TEAEs at RP2D were transient and reversible cytopenias (neutropenia [69.2%], anemia [57.7%]) and nausea (57.7%). No prolonged cytopenias occurred. All inflammatory AEs were transient and fully reversible. Cytokine release syndrome (CRS) was grade 1 or 2, except for one grade 3 event at RP2D that resolved in 1 day (table 1). One grade 1 ICANS event occurred and resolved within 3 days.At 6 months post-infusion, all but 1 efficacy-evaluable patient at RP2D showed resolution of clinical symptoms; patients had a median 10-point reduction in SLEDAI-2K and 1.7-point reduction in PGA score from baseline at RP2D (figure 1). Most (92%) patients at RP2D remained off chronic immunosuppressants.Robust CAR T cell expansion and complete peripheral B-cell depletion were observed, with primarily naive repopulating B cells (figure 2). Anti-dsDNA autoantibody titers decreased over time.Abstract S15:01 Figures and TableConclusions These findings demonstrate manageable safety of BMS-986353 and highlight its potential to drive immune reset, leading to sustained drug-free disease control in severe, refractory SLE. Phase 2 Breakfree-SLE trial ( NCT07015983) is currently enrolling patients.",
  "authors": [
    {
      "affiliations": [
        "Charité Universitaetsmedizin Berlin – Campus Mitte, Berlin, Germany"
      ],
      "name": "David Simon"
    },
    {
      "affiliations": [
        "Icahn School of Medicine at Mount Sinai, New York, NY, USA"
      ],
      "name": "Margrit Wiesendanger"
    },
    {
      "affiliations": [
        "University Hospitals Leuven, Leuven, Belgium"
      ],
      "name": "Ellen De Langhe"
    },
    {
      "affiliations": [
        "Mayo Clinic, Jacksonville, FL, USA"
      ],
      "name": "Vikas Majithia"
    },
    {
      "affiliations": [
        "Columbia University Irving Medical Center, New York, NY, USA"
      ],
      "name": "Anca Askanase"
    },
    {
      "affiliations": [
        "Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany"
      ],
      "name": "Georg Schett"
    },
    {
      "affiliations": [
        "NYU Grossman School of Medicine, New York, NY, USA"
      ],
      "name": "Amit Saxena"
    },
    {
      "affiliations": [
        "Overlook Medical Center, Summit, NJ, USA",
        "Atlantic Medical Group, Atlantic Health System, Morristown, NJ, USA"
      ],
      "name": "Neil Kramer"
    },
    {
      "affiliations": [
        "Providence Swedish Medical Center and University of Washington School of Medicine, Seattle, WA, USA"
      ],
      "name": "Philip Mease"
    },
    {
      "affiliations": [
        "Department of Internal Medicine II, University of Würzburg, Würzburg, Germany"
      ],
      "name": "Marc Schmalzing"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, NJ, USA"
      ],
      "name": "Alisha Desai"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, NJ, USA"
      ],
      "name": "Alexis Melton"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, NJ, USA"
      ],
      "name": "Brandon M Law"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, NJ, USA"
      ],
      "name": "Whitney Handy"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, NJ, USA"
      ],
      "name": "Griff Mctume"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, NJ, USA"
      ],
      "name": "Takafumi Ide"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, NJ, USA"
      ],
      "name": "Melissa Harnois"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, NJ, USA"
      ],
      "name": "Jerill Thorpe"
    },
    {
      "affiliations": [
        "Bristol Myers Squibb, Princeton, NJ, USA"
      ],
      "name": "Ashley Koegel"
    },
    {
      "affiliations": [
        "Cleveland Clinic, Cleveland, OH, USA"
      ],
      "name": "Emily Littlejohn"
    }
  ],
  "title": "S15:01 Safety and efficacy of CD19 NEX-T® (BMS-986353)—a CD19-directed chimeric antigen receptor (CAR) T cell therapy—for severe refractory systemic lupus erythematosus (SLE): breakfree-1 trial update",
  "uid": "bab09183-9a4f-50c9-b97b-0b915ad52722"
}