{
  "abstract": "Introduction Systemic sclerosis (SSc) is a severe autoimmune disease in which disease-specific autoantibodies implicate plasma cells as central drivers of pathogenesis. First clinical observations suggest that BCMA×CD3 bispecific antibody therapy with teclistamab can achieve effective plasma and B cell depletion, yet systematic data from larger cohorts are lacking.Material and Methods Patients with severe and progressive SSc unresponsive to at least two immunosuppressive therapies were treated with teclistamab using a step-up regimen (0.06 mg/kg day 1, 0.3 mg/kg day 3, 1.5 mg/kg days 5, 14, 21, 28). All immunosuppressive and antifibrotic therapies were discontinued at least 2 weeks before initiation. We report all safety data during the follow-up period, with efficacy data reported only for patients who are treated for longer than four weeks.Results Four patients (median age 51.5 years (IQR 45.25-57), median disease duration 2 years (IQR 1.5-3.5) were treated with teclistamab ( table 1). 3/4 patients suffered from interstitial lung disease and SSc heart disease, respectively.Teclistamab was generally well tolerated; no immune effector cell-associated neurotoxicity syndrome (ICANS) occurred with only mild cytokine release syndrome (CRS) (one patient with CRS grade 2; three with CRS 1). 4/4 patients developed infections that resolved with antibiotics and did not require hospitalization. 3/4 patients developed hypogammaglobulinemia and 2/4 received IVIG substitution when immunoglobulin G level fell below < 4 g/L.Three patients met the criteria for the efficacy analysis (>4 weeks follow-up). Of those three patients all showed an improvement of skin disease with a mean improvement of 14/51 (+/- 9) at the last follow-up. There was also a rapid improvement in cardiac disease in both affected patients with a mean fall in NT-proBNP of 326 ng/L (+/- 146) and a mean fall in troponin T of 67 ng/L (+/- 35). One patient with concomitant immune thrombocytopenia exhibited sustained normalization of platelet counts.Flow cytometry of peripheral blood and bone marrow indicated a complete eradication of CD38+CD138+ plasma cells and CD20+ B cells by week 2 and 8, respectively. 2/3 of patients experienced a concomitant decline in autoantibody titers by week three and complete and sustained seroconversion of patient 1 by week 28.Conclusions This case series substantiates previous single-patient observations by demonstrating that teclistamab induces effective plasma and B cell depletion with early clinical signals in severe and refractory SSc. These findings underscore the need for clinical trials to assess long-term efficacy and durability of teclistamab therapy in SSc.Abstract P.252 Table 1Patients’ characteristics, safety and efficacy at last follow-up",
  "authors": [
    {
      "affiliations": [
        "Charité - Universitätsmedizin Berlin, Departement for Rheumatology and Clinical Immunology, Berlin, Germany"
      ],
      "name": "Elpida Phithak"
    },
    {
      "affiliations": [
        "Charité - Universitätsmedizin Berlin, Departement for Rheumatology and Clinical Immunology, Berlin, Germany"
      ],
      "name": "Robert Biesen"
    },
    {
      "affiliations": [
        "Charité - Universitätsmedizin Berlin, Departement for Rheumatology and Clinical Immunology, Berlin, Germany"
      ],
      "name": "Fredrik Albach"
    },
    {
      "affiliations": [
        "Charité - Universitätsmedizin Berlin, Departement for Rheumatology and Clinical Immunology, Berlin, Germany"
      ],
      "name": "Ioanna Minopolou"
    },
    {
      "affiliations": [
        "Charité - Universitätsmedizin Berlin, Departement for Rheumatology and Clinical Immunology, Berlin, Germany",
        "German Rheumatism Research Centre (DRFZ) Berlin, a Leibnitz Institute, Berlin, Germany"
      ],
      "name": "Arnd Kleyer"
    },
    {
      "affiliations": [
        "Charité - Universitätsmedizin Berlin, Departement for Rheumatology and Clinical Immunology, Berlin, Germany"
      ],
      "name": "Edgar Wiebe"
    },
    {
      "affiliations": [
        "Charité - Universitätsmedizin Berlin, Departement for Rheumatology and Clinical Immunology, Berlin, Germany"
      ],
      "name": "Marie Rehm"
    },
    {
      "affiliations": [
        "German Rheumatism Research Centre (DRFZ) Berlin, a Leibnitz Institute, Berlin, Germany"
      ],
      "name": "Qingyu Cheng"
    },
    {
      "affiliations": [
        "Charité - Universitätsmedizin Berlin, Departement for Rheumatology and Clinical Immunology, Berlin, Germany"
      ],
      "name": "Arne Sattler"
    },
    {
      "affiliations": [
        "German Rheumatism Research Centre (DRFZ) Berlin, a Leibnitz Institute, Berlin, Germany"
      ],
      "name": "Stefano Bianco"
    },
    {
      "affiliations": [
        "Charité - Universitätsmedizin Berlin, Departement for Rheumatology and Clinical Immunology, Berlin, Germany"
      ],
      "name": "Anja Fleischmann"
    },
    {
      "affiliations": [
        "Charité - Universitätsmedizin Berlin, Departement for Rheumatology and Clinical Immunology, Berlin, Germany",
        "German Rheumatism Research Centre (DRFZ) Berlin, a Leibnitz Institute, Berlin, Germany",
        "Fraunhofer Institute for Translational Medicine and Pharmacology, Allergology and Immunology, Berlin, Germany"
      ],
      "name": "Gerhard Krönke"
    },
    {
      "affiliations": [
        "Charité - Universitätsmedizin Berlin, Departement for Rheumatology and Clinical Immunology, Berlin, Germany",
        "German Rheumatism Research Centre (DRFZ) Berlin, a Leibnitz Institute, Berlin, Germany",
        "Fraunhofer Institute for Translational Medicine and Pharmacology, Allergology and Immunology, Berlin, Germany"
      ],
      "name": "Tobias Alexander"
    },
    {
      "affiliations": [
        "Charité - Universitätsmedizin Berlin, Departement for Rheumatology and Clinical Immunology, Berlin, Germany",
        "German Rheumatism Research Centre (DRFZ) Berlin, a Leibnitz Institute, Berlin, Germany"
      ],
      "name": "David Simon"
    },
    {
      "affiliations": [
        "Charité - Universitätsmedizin Berlin, Departement for Rheumatology and Clinical Immunology, Berlin, Germany"
      ],
      "name": "Elise Siegert"
    }
  ],
  "title": "P.252 BCMAXCD3 bispecific antibody therapy with teclistamab induces profound B- and plasma cell depletion with preliminary clinical efficacy in the treatment of refractory systemic sclerosis - a case series",
  "uid": "f931023e-c69d-58ad-a0fc-01b5bdb4a526"
}