{
  "abstract": "Introduction Convincing data support targeting B-cells in systemic sclerosis. This has led to investigate anti-CD19 CAR T-cells that showed promises. However, CAR-T have concerns including high costs, manufacturing, viral transfection with long-term safety questions and a heavy conditioning. Blinatumomab, a bispecific T-cell engager targeting CD3 and CD19, may offer a simpler and more affordable strategy to obtain profound B-cell depletion. We aimed at evaluating blinatumomab in refractory patients.Material and Methods Patients with refractory disease and anti-Scl70 autoantibodies were considered for treatment with blinatumomab following a multidisciplinary review to validate its off-label use. The treatment included hydrocortisone (100 mg), acetaminophen (1 g), and dexchlorpheniramine (5 mg), followed by continuous infusion of blinatumomab at 9 µg/day for 7 days, then 28 µg/day for another 7 days. Patients were closely monitored in hospital setting throughout the intravenous treatment phase and then ambulatorily.Results Five patients were included: 4 women (P1, P2, P3, P4) and one man (P5) of median age 64 (IQR : 61-65) years. All patients had recent and progressive SSc, and were considered refractory after a median use of 4 immunosuppressive therapies (3-8). The baseline median modified Rodnan skin score (mRSS) was 16 (15-23). All patients had interstitial lung disease with a median forced vital capacity (FVC) of 61% (28-79); 4 had cardiac fibrosis on imaging and one had pulmonary hypertension.At the time of abstract submission, all patients had received the complete treatment. During infusion, 4 patients developed a grade 1 cytokine release syndrome treated with acetaminophen, and one a grade 2 treated with acetaminophen and fluids without need for tocilizumab. No Immune Effector Cell-Associated Neurotoxicity Syndrome was observed.All patient completed month 1 of follow-up, 2 completed month 3 and 1 month 6. Peripheral B-cell depletion was complete by day 3 and B cell repopulation was seen at month 1 (figure 1A). All patients remained above the lower limit for total IgG (figure 1B). There was no impact on post-vaccination serologies, and no severe infections occurred. Auto-antibodies remained unchanged, but there was a marked reduction in the type I interferon signature. B-cell receptor (BCR) sequencing is underway.Clinically, all patients reported a general improvement in symptoms at month 1. A decrease in mRSS was observed in the two patients who completed the 3-month follow-up (figure 2A). FVC improved after treatment (figure 2B).Conclusions This series suggests that blinatumomab is safe although given to severe and refractory patients. Preliminary data suggest some short-term benefits.Abstract OC.53 Figure 1",
  "authors": [
    {
      "affiliations": [
        "Rheumatology Department, Cochin Hospital, Université Paris Cité, Paris, France"
      ],
      "name": "Jerome Avouac"
    },
    {
      "affiliations": [
        "Rheumatology Department, CHU Strasbourg, Strasbourg, France"
      ],
      "name": "Marc Scherlinger"
    },
    {
      "affiliations": [
        "Haematology Department, Cochin Hospital, Université Paris Cité, Paris, France"
      ],
      "name": "Justine Decroocq"
    },
    {
      "affiliations": [
        "Rheumatology Department, CHU Strasbourg, Strasbourg, France"
      ],
      "name": "Yannick Dieudonne"
    },
    {
      "affiliations": [
        "Rheumatology Department, Cochin Hospital, Université Paris Cité, Paris, France"
      ],
      "name": "Stephane Hilliquin"
    },
    {
      "affiliations": [
        "Rheumatology Department, Cochin Hospital, Université Paris Cité, Paris, France"
      ],
      "name": "Roberto d’Alessandro"
    },
    {
      "affiliations": [
        "Pharmacy, Cochin Hospital, Université Paris Cité, Paris, France"
      ],
      "name": "Marie Laure Brandely-Piat"
    },
    {
      "affiliations": [
        "Pharmacy, CHU Strasbourg, Strasbourg, France"
      ],
      "name": "Anne El Aatmani"
    },
    {
      "affiliations": [
        "Haematology Department, Cochin Hospital, Université Paris Cité, Paris, France"
      ],
      "name": "Didier Bouscary"
    },
    {
      "affiliations": [
        "Rheumatology Department, CHU Strasbourg, Strasbourg, France"
      ],
      "name": "Emmanuel Chatelus"
    },
    {
      "affiliations": [
        "Internal Medicine Department, CHU Strasbourg, Strasbourg, France"
      ],
      "name": "Thierry Martin"
    },
    {
      "affiliations": [
        "Rheumatology Department, CHU Strasbourg, Strasbourg, France"
      ],
      "name": "Jean Sibilia"
    },
    {
      "affiliations": [
        "Rheumatology Department, CHU Strasbourg, Strasbourg, France"
      ],
      "name": "Yannick Allanore"
    }
  ],
  "title": "OC.53 Use of the CD19/CD3 T cell engager blinatumomab in refractory systemic sclerosis: a case series",
  "uid": "f3c007a4-33d9-5329-b1d8-75c5e2edeef2"
}