1. Conferences Overview
    2. Deutscher Rheumatologiekongress 2025
    3. Targeting the plasma cell niche in systemic sclerosis: A case series exploring efficacy and safety of the bispecific T cell engaging anti-BCMAxCD3 antibody teclistamab in severe, treatment refractory patients
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Deutscher Rheumatologiekongress 2025

53. Kongress der Deutschen Gesellschaft für Rheumatologie und Klinische Immunologie (DGRh)
39. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)
17.-20.09.2025
Wiesbaden


Meeting Abstract

Targeting the plasma cell niche in systemic sclerosis: A case series exploring efficacy and safety of the bispecific T cell engaging anti-BCMAxCD3 antibody teclistamab in severe, treatment refractory patients

Wolfgang Merkt 1
Andrea-Hermina Györfi 1
Ayla Stütz 1
Christina Düsing 1
Laura-Marie Lahu 1
Franca Sophie Deicher 1
Marie Celine van Saan 1
Alexandru-Emil Matei 1
Alexander Hölscher 1
Manuel Röhrich 1
Mareike Cramer 1
Bernhard Homey 1
Björn Bühring 2
Alexander Kreuter 3
Aleksandar Radujkovic 1
Claus Peter Heußel 4
Hanns-Martin Lorenz 4
Ricardo Grieshaber-Bouyer 5
Georg Schett 5
Jörg Distler 1
1University Hospital Düsseldorf, Düsseldorf
2Krankenhaus St. Josef, Wuppertal
3HELIOS St. Elisabeth Clinic Oberhausen, Oberhausen
4University Hospital Heidelberg, Heidelberg
5Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen

Text

Introduction: 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 1 autoantibodies [1], [2], [3], [4].

Methods: We treated 3 high-risk cases of severe treatment-refractory diffuse cutaneous SSc (dcSSc) with the plasma cell-depleting antibody teclistamab. After 6 doses of teclistamab (3 step up doses followed by 3 full doses every other week), 1 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 >6 months.

Results: The 1st patient showed improvement of modified Rodnan skin score (mRSS) from 21 to 10, diffusion capacity for carbon monoxide (DLCO) stabilized (52% vs. 48% at BL) with no further radiological progress of interstitial lung disease (ILD). Complications on follow-up included relapse of his arterial fibrillation, first diagnosis of pulmonary arterial hypertension and histologic diagnosis of pulmonary carcinoma 7 months after BL.

The 2nd patient showed improvement of mRSS from 22 to 13, tendon friction rubs (TFR) resolved. DLCO remained stable (70% vs. 76% at BL) and indices of ground glass opacities (GGOI, 16% vs. 20%) and reticular changes (FIBI, 16% vs. 23%) on HRCT slightly regressed. Heart involvement improved as evidenced by a decline in high-sensitive TroponinT (hsTnT 23 vs. 95 ng/l at BL). He regained 15kg body weight.

The 3rd patient showed improvement of mRSS from 28 to 20, TFR resolved. DLCO (92% vs. 91% at BL), GGOI (34% vs. 33%) and FIBI (38% vs. 43%) remained stable. hsTnT remained stable (19 ng/l vs. 35 ng/l at BL). Further outcomes: Teclistamab reduced anti-topoisomerase I autoantibodies by an average of >92%. Teclistamab was associated with cytokine release syndrome (1st patient: CRS1+3, 2nd and 3rd patient: CRS2), hypogammaglobulinemia and mild infections (despite regular immunoglobulin replacement). Patient 2 and 3 reported a significant increase in the quality of life.

Conclusion: Teclistamab may be effective as a salvage therapy in severe, treatment-refractory dcSSc, even with advanced disease. A longer observation and further studies are required to identify SSc populations with optimal benefit-risk profiles.

Table 1 [Tab. 1]

Table 1

Literatur

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[2] Auth J, Müller F, Völkl S, Bayerl N, Distler JHW, Tur C, Raimondo MG, Chenguiti Fakhouri S, Atzinger A, Coppers B, Eckstein M, Liphardt AM, Bäuerle T, Tascilar K, Aigner M, Kretschmann S, Wirsching A, Taubmann J, Hagen M, Györfi AH, Kharboutli S, Krickau T, Dees C, Spörl S, Rothe T, Harrer T, Bozec A, Grieshaber-Bouyer R, Fuchs F, Kuwert T, Berking C, Horch RE, Uder M, Mackensen A, Schett G, Bergmann C. CD19-targeting CAR T-cell therapy in patients with diffuse systemic sclerosis: a case series. Lancet Rheumatol. 2025 Feb;7(2):e83-e93. DOI: 10.1016/S2665-9913(24)00282-0
[3] Bergmann C, Müller F, Distler JHW, Györfi AH, Völkl S, Aigner M, Kretschmann S, Reimann H, Harrer T, Bayerl N, Boeltz S, Wirsching A, Taubmann J, Rösler W, Spriewald B, Wacker J, Atzinger A, Uder M, Kuwert T, Mackensen A, Schett G. Treatment of a patient with severe systemic sclerosis (SSc) using CD19-targeted CAR T cells. Ann Rheum Dis. 2023 Aug;82(8):1117-20. DOI: 10.1136/ard-2023-223952
[4] Merkt W, Lorenz HM, Schmitt M. CAR T-Cell Therapy in Autoimmune Disease. N Engl J Med. 2024 May 2;390(17):1628-9. DOI: 10.1056/NEJMc2403705