25rhk204 10.3205/25rhk204 urn:nbn:de:0183-25rhk2044 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 Merkt Merkt Wolfgang W
University Hospital Düsseldorf, Düsseldorf
author Györfi Györfi Andrea-Hermina AH
University Hospital Düsseldorf, Düsseldorf
author Stütz Stütz Ayla A
University Hospital Düsseldorf, Düsseldorf
author Düsing Düsing Christina C
University Hospital Düsseldorf, Düsseldorf
author Lahu Lahu Laura-Marie LM
University Hospital Düsseldorf, Düsseldorf
author Deicher Deicher Franca Sophie FS
University Hospital Düsseldorf, Düsseldorf
author van Saan van Saan Marie Celine MC
University Hospital Düsseldorf, Düsseldorf
author Matei Matei Alexandru-Emil AE
University Hospital Düsseldorf, Düsseldorf
author Hölscher Hölscher Alexander A
University Hospital Düsseldorf, Düsseldorf
author Röhrich Röhrich Manuel M
University Hospital Düsseldorf, Düsseldorf
author Cramer Cramer Mareike M
University Hospital Düsseldorf, Düsseldorf
author Homey Homey Bernhard B
University Hospital Düsseldorf, Düsseldorf
author Bühring Bühring Björn B
Krankenhaus St. Josef, Wuppertal
author Kreuter Kreuter Alexander A
HELIOS St. Elisabeth Clinic Oberhausen, Oberhausen
author Radujkovic Radujkovic Aleksandar A
University Hospital Düsseldorf, Düsseldorf
author Heußel Heußel Claus Peter CP
University Hospital Heidelberg, Heidelberg
author Lorenz Lorenz Hanns-Martin HM
University Hospital Heidelberg, Heidelberg
author Grieshaber-Bouyer Grieshaber-Bouyer Ricardo R
Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen
author Schett Schett Georg G
Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen
author Distler Distler Jörg J
University Hospital Düsseldorf, Düsseldorf
author German Medical Science GMS Publishing House
Düsseldorf
 610 20250917 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). M0627 204 Deutsche Gesellschaft für Rheumatologie Deutsche Gesellschaft für Orthopädische Rheumatologie 53. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 39. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh) Deutscher Rheumatologiekongress 2025 Vaskulitiden & Kollagenosen Wiesbaden 20250917 20250920 VK.55 TextIntroduction: 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 , , , .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 Merkt W Freitag M Claus M Kolb P Falcone V Röhrich M Rodon L Deicher F Andreeva I Tretter T Tykocinski LO Blank N Watzl C Schmitt A Sauer T Müller-Tidow C Polke M Heußel CP Dreger P Lorenz HM Schmitt M Third-generation CD19.CAR-T cell-containing combination therapy in Scl70+ systemic sclerosis 2024 Ann Rheum Dis 543-6 Merkt W, Freitag M, Claus M, Kolb P, Falcone V, Röhrich M, Rodon L, Deicher F, Andreeva I, Tretter T, Tykocinski LO, Blank N, Watzl C, Schmitt A, Sauer T, Müller-Tidow C, Polke M, Heußel CP, Dreger P, Lorenz HM, Schmitt M. Third-generation CD19.CAR-T cell-containing combination therapy in Scl70+ systemic sclerosis. Ann Rheum Dis. 2024 Mar 12;83(4):543-6. DOI: 10.1136/ard-2023-225174 http://dx.doi.org/10.1136/ard-2023-225174 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 2025 Lancet Rheumatol e83-e93 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 http://dx.doi.org/10.1016/S2665-9913(24)00282-0 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 2023 Ann Rheum Dis 1117-20 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 http://dx.doi.org/10.1136/ard-2023-223952 Merkt W Lorenz HM Schmitt M CAR T-Cell Therapy in Autoimmune Disease 2024 N Engl J Med 1628-9 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 http://dx.doi.org/10.1056/NEJMc2403705 11
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