Background: Systemic sclerosis (SSc) is a severe autoimmune disease in which B cells are involved in both the dysregulation of the immune system that triggers the disease and the persistent tissue fibrosis. However, B cell-depleting therapies have led to inconsistent clinical results, which may relate to insufficient B cell depletion.

Objectives: To report the latest data from a case series in which patients with SSc who do not respond to conventional therapies are treated with the bispecific CD3/CD19 antibody blinatumomab.

Methods: Patients with rapidly progressing severe SSc despite intensive therapy are treated with four cycles (2 x 9 µg/d for 5 days, 1 x 28 µg/d for 5 days, 1 x 28 µg/d for 10 days) of blinatumomab. Safety and efficacy are evaluated.

Results: So far, three patients have completed the treatment. The first patient, a 35-year-old woman with onset of symptoms 16 months ago, Raynaud’s syndrome, puffy fingers, fingertip ulcerations, polyarticular joint pain, progressive skin stiffness on the hands, feet and forearms, cardiac fibrosis, typical SSc capillaroscopy and Scl 70 antibodies (abs), tolerated the therapy well with no signs of toxicity during or after treatment. The second patient, a 36-year-old woman with Raynaud’s syndrome for 36 months and a rapid worsening of clinical symptoms after the birth of her first child four months prior to enrollment in the study (progressive skin stiffness in the hands, feet, forearms and décolleté, puffy fingers, polyarticular joint pain, pulmonary fibrosis, typical SSc capillaroscopy and Scl70 abs), also had no cytokine release or neurotoxicity, but developed neutropenia in the first and after completion of the third cycle which resolved after 7 days. No significant changes in neutrophil counts occurred during the second and fourth cycle. The third patient, a 39 year-old men with Raynaud’s syndrome for 60 months, pitting scars, systemic lymphadenopathy and a rapidly progressing pulmonary fibrosis tolerated treatment remarkably well without any signs of toxicity. In all patients, peripheral B cell counts declined completely from the first day of treatment. The B cells recovered to normal levels three weeks after treatment. Peripheral T cells were significantly reduced on the first day of treatment, but quickly recovered to normal levels and remained stable during subsequent cycles. IgG and Scl 70 abs levels temporarily decreased after treatment. Already during the first cycle, all patients reported an improvement in clinical symptoms. After treatment, their fingers were no longer swollen, peripheral arthralgias, restricted arm movement and skin stiffness had disappeared. The mRSS decreased after treatment and FAPI-PET showed complete resolution of fibrocyte activity and tissue fibrosis. Remarkably, despite reconstitution of peripheral B cells and reappearance of Scl 70 abs, all patients remain in sustained clinical remission with no signs of disease activity.

Conclusion: We present the first cases worldwide in which blinatumomab was used as a B-cell-depleting therapy in a non-malignant disease. Blinatumomab was safe with transient neutropenia in one of the three patients and resulted in profound B-cell depletion and a significant decrease in serum IgG. Remarkably, this did not lead to increased susceptibility to infections. Clinically, the therapy led to a rapid and sustained improvement in symptoms. Further studies are needed to determine the value of B-cell depleting therapy with blinatumomab in SS.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Christina Gebhardt: None declared, Franziska Szelinski: None declared, Hector Rincon-Arevalo: None declared, Guilia Magno: None declared, Veit Buecklein: None declared, Gerulf Haenel: None declared, Gerhard Zugmaier Amgen, Michael Bergwelt: None declared, Marion Subklewe: None declared, Thomas Dörner: None declared, Alla Skapenko: None declared, Hendrik Schulze-Koops: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.