Targeting the plasma cell niche in systemic sclerosis: A case series about the bispecific anti-BCMAxCD3 antibody teclistamab in severe, treatment-refractory patients

Andrea-Hermina Györfi¹, Ayla Nadja Stuetz², Christina Duesing³, Laura-Marie Lahu⁴, Franca Sophie Deicher⁵, Yi-Nan Li⁶, Celine van Saan⁵, Alexandru-Emil Matei⁷, Alexander Hoelscher⁵, Peter-Martin Bruch⁸, Sarah Koziel⁸, Manuel Roehrich⁹, Mareike Cramer¹⁰, Bernhard Homey⁵, Bjoern Buehring¹¹, Alexander Kreuter¹², Aleksandar Radujkovic⁵, Claus Peter Heußel¹³, Hanns-Martin Lorenz¹⁴, Ricardo Grieshaber-Bouyer¹⁵, Georg Schett¹⁶, Jörg Distler¹⁷ and Wolfgang Merkt¹⁸, ¹Department of Rheumatology, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University., Düsseldorf, Germany, ²Department of Rheumatology, University Hospital Düsseldorf, Medical Faculty of Heinrich-Heine University. Hiller Research Center, University Hospital Düsseldorf, Medical Faculty of Heinrich-Heine University, Düsseldorf, Nordrhein-Westfalen, Germany, ³Klinik für Rheumatologie, Düsseldorf, Germany, ⁴Department of Rheumatology, University Hospital Düsseldorf, Medical Faculty of Heinrich-Heine University. Hiller Research Center, University Hospital Düsseldorf, Medical Faculty of Heinrich-Heine University, Düsseldorf, Germany, ⁵Uniklinik Düsseldorf, Düsseldorf, Germany, ⁶University Hospital of Düsseldorf, Düsseldorf, Germany, ⁷Department of Rheumatology, University Hospital Düsseldorf, Medical Faculty of Heinrich-Heine University. Hiller Research Center, University Hospital Düsseldorf, Medical Faculty of Heinrich-Heine University. Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, and Fraunhofer Cluster of Excellence for Immune Mediated Diseases CIMD, Frankfurt am Main, Germany, Düsseldorf, Germany, ⁸University Hospital Düsseldorf, Dusseldorf, Germany, ⁹Universitätsmedizin Mainz, Mainz, ¹⁰University Hospital Düsseldorf, Düsseldorf, Germany, ¹¹Bergisches Rheuma-Zentrum, Krankenhaus St Josef, Wuppertal, Germany, ¹²HELIOS St. Elisabeth Clinic Oberhausen, University Witten-Herdecke, Oberhausen, Germany, ¹³Thoraxklinik, University of Heidelberg, Heidelberg, ¹⁴Universitétsklinikum Heidelberg, Heidelberg, Germany, ¹⁵University Hospital Erlangen, Erlangen, Germany, ¹⁶Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany, Erlangen, Germany, ¹⁷University Hospital Duesseldorf and HHU, Duesseldorf, Germany, ¹⁸University Hospital Düsseldorf, Düsseldorf, Germany

Meeting: ACR Convergence 2025

Keywords: autoimmune diseases, interstitial lung disease, skin, Systemic sclerosis, Therapy, alternative

Session Information

Date: Sunday, October 26, 2025

Title: (0671–0710) Systemic Sclerosis & Related Disorders – Clinical Poster I

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: Systemic sclerosis (SSc) possesses the highest case-related mortality of all rheumatic diseases. B cell-targeting, including CD19-targeting CAR-T cells, has shown efficacy but failed to eliminate the SSc-specific anti-topoisomerase-I autoantibodies. 1-4

Methods: We treated three high-risk cases of severe treatment-refractory diffuse cutaneous SSc (dcSSc) with the plasma cell-depleting antibody teclistamab (Table 1). After six cycles of teclistamab, one cycle of rituximab was administered to block recovery of autoantibody-producing cells. All patients were anti-topoisomerase-I antibody positive and have not responded sufficiently to multiple immunosuppressive therapies. Immunosuppressive and antifibrotic therapies were discontinued prior to baseline (BL). Patients were followed for more than six months.

Results: Treatment with teclistamab depleted all plasma cells in the skin. Anti-topoisomerase-I-autoantibody titers seroconverted in two patients and dropped by 83% in the third patient. This immunological response was associated with a decrease of the modified Rodnan skin score, stabilization of SSc-ILD, resolution of tendon friction rubs and decreases in the EUSTAR-AI. The effect on SSc-associated primary myocardial involvement was heterogeneous. Treatment with teclistamab was associated with several adverse events including cytokine release syndrome, hypogammaglobulinemia and mild infections (despite regular immunoglobulin replacement).

Conclusion: Teclistamab may offer potential as a rescue therapy for selected patients suffering from severe, treatment-refractory dcSSc, even with advanced disease.

Table 1. Patient characteristics at baseline.

Abbreviations: Scl-70 Ab, anti-topoisomerase-I (Scl70) autoantibodies; mRSS, modified Rodnan Skin Score; TFR, tendon friction rubs; ILD, interstitial lung disease; SSc-pHI, systemic sclerosis primary heart involvement

Image 1. Selected clinical outcomes

(modified Rodnan skin score, mRSS; EUSTAR activity index, AI).

Image 2. Immunological outcomes

(serological anti-topoisomerase-I titres and multi-color immunofluorescence stainings of skin biopsies from patient 3 using CODEX; DAPI stains nuclei, CD3 stains T cells and CD20, PAX5 and CD138 stain B cells and plasma cells, respectively)

Disclosures: A. Györfi: AbbVie, 6, Boehringer-Ingelheim, 6; A. Stuetz: None; C. Duesing: None; L. Lahu: None; F. Deicher: None; Y. Li: None; C. van Saan: None; A. Matei: None; A. Hoelscher: None; P. Bruch: None; S. Koziel: None; M. Roehrich: None; M. Cramer: None; B. Homey: None; B. Buehring: None; A. Kreuter: None; A. Radujkovic: None; C. Heußel: None; H. Lorenz: None; R. Grieshaber-Bouyer: AstraZeneca, 1, Candid Therapeutics, 1, Cullinan Therapeutics, 1, Eli Lilly, 6; G. Schett: Cabaletta, 6, Eli Lilly, 6, Janssen, 6, Kyverna, 6, Novartis, 6, UCB, 6; J. Distler: 4D Science, 8, 11, Actelion, 2, 6, Active Biotech, 2, 6, Anamar, 2, 6, Array Biopharma, 2, 6, ARXX Therapeutics, 2, 6, aTyr Pharma, 2, 6, Bayer Pharma, 2, 6, BMS (Bristol-Myers Squibb), 2, 6, Boehringer Ingelheim, 2, 6, Celgene, 2, 6, FibroCure, 4, Galapagos, 2, 6, GSK, 2, 6, Inventiva, 2, 6, JB Therapeutics, 2, 6, Medac, 2, 6, Novartis, 2, 6, Pfizer, 2, 6, Redx Pharma, 2, 6, RuiYi, 2, 6, Sanofi-Aventis, 2, 6, UCB, 2, 6; W. Merkt: Boehringer-Ingelheim, 6, Bristol-Myers Squibb(BMS), 5, Evotec, 5, Glapagos, 12, support for congress travel, Kyverna, 6, Lilly, 12, support for congress travel.

To cite this abstract in AMA style:

Györfi A, Stuetz A, Duesing C, Lahu L, Deicher F, Li Y, van Saan C, Matei A, Hoelscher A, Bruch P, Koziel S, Roehrich M, Cramer M, Homey B, Buehring B, Kreuter A, Radujkovic A, Heußel C, Lorenz H, Grieshaber-Bouyer R, Schett G, Distler J, Merkt W. Targeting the plasma cell niche in systemic sclerosis: A case series about the bispecific anti-BCMAxCD3 antibody teclistamab in severe, treatment-refractory patients [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/targeting-the-plasma-cell-niche-in-systemic-sclerosis-a-case-series-about-the-bispecific-anti-bcmaxcd3-antibody-teclistamab-in-severe-treatment-refractory-patients/. Accessed .

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