{
  "abstract": "Objectives To report initial safety, efficacy, pharmacokinetics (PK) and biomarker analyses in patients with srSLE, treated with obe-cel in the ongoing open-label CARLYSLE study ( NCT06333483).Methods Eligible patients (12–65 years) had srSLE diagnosis per 2019 EULAR/ACR criteria, SLEDAI-2K score ≥8-points at screening with ≥1 major SLE-related organ involvement and were refractory to standard therapies. Obe-cel was administered as a single flat dose of either 50×10 6 (50M) or 100×106 (100M) CAR T-cells. Primary endpoints: dose-limiting toxicities (DLTs) within 28 days of infusion, adverse event frequency. Secondary endpoints: Definition of Remission in SLE (DORIS), SLEDAI-2K, renal response, biomarkers, PK and pharmacodynamics.Results As of 04 November 2025, 13 patients were enrolled; nine adults were infused with obe-cel 50M (n=6; median follow-up: 11.4 months) or 100M (n=3; median follow-up: 3.3 months). Three adolescents were enrolled and one adult withdrew prior to infusion. Data from nine infused adults are presented. At baseline, both 50M and 100M cohorts had active srSLE (median SLEDAI-2K score: 17.0 and 18.0) and lupus nephritis was present in 6/6 and 2/3 patients, respectively.No immune effector cell-associated neurotoxicity syndrome, or Grade ≥2 cytokine release syndrome events were observed (table 1). One case of liver injury was observed (fully resolved), and was possibly related to CAR T-cell activity/concomitant medication-related toxicity (anti-infective prophylaxis) and therefore considered a DLT. In the 50M cohort: 5/6 (83.3%) patients achieved DORIS (median onset: 5.1 months); complete and partial renal response (CRR/PRR) was achieved by 3/6 (50.0%) patients (Month 1) and 1/6 (16.7%) patients (Month 7), respectively. The follow-up length was insufficient to calculate DORIS response or CRR/PRR for the 100M cohort. Clinically meaningful reductions in SLEDAI-2K (figure 1) were observed in all patients.Robust CAR T-cell expansion was observed and median time to loss of persistence was ‘≤3.0 months. All patients showed deep B-cell depletion post-infusion; >90% of reconstituted B-cells at time of recovery (median: 6.0 months) were transitional and naïve (50M cohort).Abstract LBS1:02 Figure 1Change in SLEDAI-2K score over time in adult patients infused with obe-cel at the 50M or 100M doseAbstract LBS1:02 Table 1Safety outcomes in adult patients infused with obe-cel at the 50M or 100M doseConclusions In these preliminary findings of obe-cel in srSLE, obe-cel demonstrated a favourable safety profile and clinical benefit despite severe baseline disease activity. Emerging data in the 100M cohort are consistent with the 50M cohort; evaluation is ongoing.",
  "authors": [
    {
      "affiliations": [
        "University College London, London, UK",
        "University College London Hospital, London, UK"
      ],
      "name": "Maria Leandro"
    },
    {
      "affiliations": [
        "University College London, London, UK",
        "University College London Hospital, London, UK",
        "Royal Free Hospital NHS Trust, London, UK"
      ],
      "name": "Ruth Pepper"
    },
    {
      "affiliations": [
        "Kellgren Centre for Rheumatology, NIHR Manchester Biomedical Research Centre, Manchester University, Manchester, UK",
        "NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK"
      ],
      "name": "Ben Parker"
    },
    {
      "affiliations": [
        "Manchester Royal Infirmary, Manchester, UK"
      ],
      "name": "Eleni Tholouli"
    },
    {
      "affiliations": [
        "Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK"
      ],
      "name": "David Jayne"
    },
    {
      "affiliations": [
        "Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK"
      ],
      "name": "Ben Uttenthal"
    },
    {
      "affiliations": [
        "Hospital Universitari Vall dHebron-Universitat Autónoma de Barcelona, Barcelona, Spain"
      ],
      "name": "Josefina Cortés-Hernández"
    },
    {
      "affiliations": [
        "Hospital Universitari Vall dHebron-Universitat Autónoma de Barcelona, Barcelona, Spain"
      ],
      "name": "Pere Barba"
    },
    {
      "affiliations": [
        "Hospital Universitari i Politècnic La Fe, Valencia, Spain"
      ],
      "name": "José Andrés Román Ivorra"
    },
    {
      "affiliations": [
        "Autolus Therapeutics, Rockville, USA"
      ],
      "name": "Yanqing Hu"
    },
    {
      "affiliations": [
        "Autolus Therapeutics, Weil am Rhein, Germany"
      ],
      "name": "Wolfram Brugger"
    },
    {
      "affiliations": [
        "Autolus Therapeutics, Basel, Switzerland"
      ],
      "name": "Silvia Basilico"
    },
    {
      "affiliations": [
        "Autolus Therapeutics, Basel, Switzerland"
      ],
      "name": "Davide Germano"
    },
    {
      "affiliations": [
        "University College London, London, UK",
        "University College London Hospital, London, UK"
      ],
      "name": "Claire Roddie"
    }
  ],
  "title": "LBS1:02 CD19-targeting chimeric antigen receptor (CAR) T-cell therapy, obecabtagene autoleucel (obe-cel), in severe refractory systemic lupus erythematosus (srSLE): initial results from phase I CARLYSLE study",
  "uid": "cb48907a-18d8-5bf7-bd31-d679b10e05dd"
}