2463: Efficacy and Safety of Car-T-Cell Treatment in Refractory Antisynthetase Syndrome – Data of the First Three Patients

Jule Taubmann¹, Johannes Knitza², Fabian Müller³, Sebastian Boeltz¹, Simon Voelkl⁴, Michael Aigner⁴, Arnd Kleyer⁵, Ioanna Minnopoulou¹, Regina Gary⁴, Sascha kretschmann⁴, Andreas Mackensen⁴ and Georg Schett⁶, ¹Department of Internal Medicine 3, Rheumatology and Immunology, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen Nürnberg, Erlangen, Germany, ²Department of Internal Medicine 3 Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany, ³Friedrich Alexander Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany, ⁴Department of Internal Medicine 5, Hematology and Oncology, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen Nürnberg, Erlangen, Germany, ⁵University Hospital Erlangen, Erlangen, Germany, ⁶Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

Background/Purpose: Antisynthetase syndrome (ASS) can be very severe affecting the lungs, the skin and the joints next to the muscles. ASS can take a refractory life-threatening course, necessitating the development of new treatment strategies. We recently reported the first case of successful rescue therapy of ASS with CD19-targeted CAR-T-cells [1]. Herein, we present efficacy and safety data for the first three patients with refractory ASS treated with autologous CD19 CAR-T-cells. The objective of this study was to test whether administration of CD19 CAR-T-cells is tolerable and effective in patients with severe refractory ASS.

Methods: Autologous CD19 CAR-T-cells were prepared and given as described previously [1,2,3]. All immunosuppressive treatments were stopped before CD19 CAR-T-cell administration. Tolerability was assessed by monitoring for Cytokine-Release Syndrome (CRS) and Immune-related effector Cell Neurotoxicity Syndrome (ICANS). Efficacy was assessed by CK levels, good response according 2016 ACR/EULAR total improvement score (TIS), imaging of muscles and lungs and successful cessation of all immunosuppressive treatments including glucocorticoids.

Results: Three ASS patients were treated with CD19 CAR-T-cells (table 1). All patients presented with active myositis and elevated CK levels. Patient 1 showed involvement of the muscles, skin and lungs, patient 2 showed involvement of muscles, skin, joints and lungs, patient 3 showed involvement of muscles and lungs. All patients did not respond to a minimum of 5 different immunosuppressive treatments (table 1). CAR-T-cell treatment was well-tolerated. Mild CRS (grade I) was observed in the first two patients. Patient 3 showed signs off increased O2 requirement (temporarily 10l/min by mask), chills and fever (39.0°C) defined as CRS grade II. All patients were treated with tocilizumab and CRS resolved quickly. Patient 2 had signs of mild self-limited ICANS (grade I discrete ataxia for a few days) two weeks after CAR-T treatment. Expansion of CAR-T-cells paralleled with the complete depletion of circulating B cells. The first two patients experienced normalization of CK levels (patient 1: CK+150 days: 70 U/l, patient 2: CK+150 days: 99 U/l), major clinical improvement according to the 2016 TIS and could stop all immunosuppressive therapy. Follow-up CT scans of the lung done in patient 1 showed resolution of alveolar inflammation. Follow-up MRI of patient 1 and 2 revealed abrogation of inflammatory changes in the thigh muscles and hamstrings. At the latest follow up (365days and 150days) both patients were in drug-free remission, while patient 3 awaits follow up assessment.

Conclusion: Taken together, these data suggest that CD19 CAR-T-cell therapy provides a possibility to intercept with severe ASS leading to drug-free remission and resolution of muscle and lung inflammation.




J. Taubmann: None; J. Knitza: None; F. Müller: AbbVie, 6, AstraZeneca, 1, 5, 6, Bristol Myers Squibb, 1, 6, Janssen, 6, KITE, 1, 6, Miltenyi Biomedicine, 1, 6, Novartis, 1, 6, Sobi, 6; S. Boeltz: None; S. Voelkl: None; M. Aigner: Kosmas Therapuetics, 8, Kyverna, 5, Miltenyi Biomedicine, 2, 7, Miltenyi Biotec, 6; A. Kleyer: None; I. Minnopoulou: None; R. Gary: None; S. kretschmann: None; A. Mackensen: BioNTech, 1, Bristol-Myers Squibb(BMS), 1, KITE/Gilead, 1, 6, Kyverna, 5, Miltenyi Biotech, 5; G. Schett: None.