Clinical efficacy and autoantibody seroconversion with CD19-CAR T cell therapy in a patient with rheumatoid arthritis and coexisting myasthenia gravis (2024)

1. Aiden Haghikia1,
2. Tobias Hegelmaier1,
3. Denise Wolleschak2,
4. Martin Böttcher2,3,
5. Vaia Pappa1,
6. Jeremias Motte4,
7. Dominic Borie5,
8. Ralf Gold4,
9. http://orcid.org/0000-0002-9872-5282Eugen Feist6,
10. http://orcid.org/0000-0001-8740-9615Georg Schett7,8,
11. http://orcid.org/0000-0002-2817-6660Dimitrios Mougiakakos2,3

1. ¹Department of Neurology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
2. ²Department of Haematology, Oncology, and Cell Therapy, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
3. ³Health Campus Immunology, Infectiology, and Inflammation, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
4. ⁴Department of Neurology, Ruhr University Bochum, Bochum, Germany
5. ⁵Kyverna Therapeutics, Emeryville, California, USA
6. ⁶Experimental Rheumatology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
7. ⁷Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-University Erlangen, Erlangen, Germany
8. ⁸Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen, Erlangen, Germany

1. Correspondence to Professor Dimitrios Mougiakakos, Department of Hematology, Oncology, and Cell Therapy, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany; dimitrios.mougiakakos{at}med.ovgu.de; Professor Aiden Haghikia, Department of Neurology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany; aiden.haghikia{at}med.ovgu.de

• Anti-Citrullinated Protein Antibodies
• Arthritis, Rheumatoid
• Autoimmune Diseases
• Autoimmunity
• B-Lymphocytes

Myasthenia gravis (MG) is a B cell-driven autoimmune disease (AID) that can coincide with rheumatoid arthritis (RA).1 Here, we report on a 37-year-old woman who was diagnosed with generalised, acetylcholine receptor (AChR)-antibody positive MG in 2013 and developed anticitrullinated protein antibody (ACPA) positive RA in 2020. Arthritis affected multiple hand and ankle joints that showed synovial swelling. Treatment was focused on controlling her severe MG, including thymectomy, acetylcholinesterase inhibitors, glucocorticoids, azathioprine, intravenous immunoglobulins, rituximab, and eculizumab. As the treatment of MG (ie, glucocorticoids, rituximab, and eculizumab) also affected RA activity, no additional RA-specific treatment had been initiated in the patient, considering the potential negative safety aspects of such combined interventions. The last treatment regimen before CD19-CAR T cell therapy was a combination of glucocorticoids (5 mg/day), eculizumab (1200 mg/biweekly), and pyridostigmine (120 mg short-acting and 90 mg long-acting/day). However, despite all of these treatments, both MG (quantitative myasthenia gravis (QMG) score: 18 (0–39); MG Activities of Daily Living (MG-ADL) score: 7 (0–24)) and RA (Disease Activity Score-28 based on erythrocyte sedimentation rate (DAS-28-ESR): 6 (0–9.4); Disease Activity Score-28 based on C reactive protein (DAS-28-CRP) 4 (0–8.6) and Clinical Disease Activity Index (CDAI): 24 (0–76)) remained active, impairing patient’s quality of life and leading to recurrent infections.

Based on previous experience in AIDs,2 we decided to proceed with a named patient approach using autologous CD19-CAR T cells engineered with a fully human second-generation anti-CD19 CAR, KYV-101 (Kyverna Therapeutics, Emeryville, California, USA). KYV-101 has been used successfully in patients with neurological AIDs such as MG and multiple sclerosis.3 4 After lymphodepletion with fludarabine (30 mg/m² from day −5 to −3) and cyclophosphamide (300 mg/m² from day −5 to −3), 1×10⁸ CAR T cells were infused. The dominance of CD4+T cells among CAR T cells …

Footnotes

• Handling editor Josef S Smolen

• X @Martin_MetabIO

• AH, TH, GS and DM contributed equally.

• Contributors AH, TH, DW, DB and DM designed the study. TH, DW, MB, JM, EF and VP acquired the data. AH, TH, MB, JM, DB, EF, RG, GS and DM interpreted the data. AH, TH, GS and DM prepared the manuscript. AH, TH, DW, MB and DM had access to and verified the data. AH and DM, as guarantors, accept full responsibility for the work and the conduct of the study, had access to the data and control the decision to publish.

• Funding AH is supported by the Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE) and the Deutsche Forschungsgemeinschaft (DFG) through the CRC Transregio 128 (Multiple Sklerose). The work of GS is supported by the DFG through the Leibniz Award and the research groups PANDORA FOR2886, CRC1483 (EmpkinS) and CRC1181. GS received further funding from the Bundesministerium für Bildung und Forschung (BMBF) through the Mascara project, the European Union through the ERC Synergy grant 4D Nanoscope and the IMI-funded project RTCure. DM is supported by the DFG through the research groups PANDORA FOR2886, CRC/TRR305 (A03), CRC/TRR221 (A06), RTG2408 (P13) and the grant 536993790.

• Competing interests AH has served on scientific advisory boards for Galapagos, Novartis and Merck Serono; received speaker honoraria from Biogen Idec, Merck Serono and Novartis; and received limited research grants from Merck Serono. DB is an employee and shareholder of Kyverna Therapeutics. EF has received speaker honoraria from AbbVie, BMS, Galapagos, Janssen, Lilly, Novartis, Roche, Sanofi and Pfizer. GS has received speaker honoraria from BMS, Cabaletta, Janssen, Kyverna, Miltenyi and Novartis. DM has received speaker honoraria and consulting fees from Abbvie, BMS, Beigene, Celgene, Galapagos, Gilead, Janssen, Miltenyi and Novartis.

• Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

• Provenance and peer review Not commissioned; externally peer reviewed.