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Background: CD19 chimeric antigen receptor (CD19-CAR) T-cell therapy has shown to induce stable drug-free remission in patients with refractory autoimmune disease (AID) [1, 2]. The management of potential relapses is currently unclear.
Case presentation: We report on a 45-year old woman with refractory Jo-1-associated anti-synthetase syndrome, presenting with myositis, arthritis, recurrent fever and severe progressive interstitial lung disease, who initially achieved remission after CD19-CAR T-cell therapy but relapsed after 9 months. CD19 CAR T-cell therapy was performed for a second time with cells cryopreserved from the original stored CAR T-cell product. However, CAR T-cells failed to expand and anti-CD19-CAR reactive T-cells were detected, which potentially led to an acute rejection of CAR T-cells before they could unfold their activity. Despite full-dose lymphodepletion, no clinical response was observed. Next, plasma cell targeting with 9 injections of the anti-CD38 antibody daratumumab was performed. Daratumumab was efficacious, but response was not sustained. The patient experienced a CMV-viremia under daratumumab, which was successfully treated with oral valganciclovir. Due to ongoing disease activity, plasma cell-targeting BCMA-CAR T-cell therapy was performed (Idecabtagene vicleucel, Bristol Myers Squibb). The patient experienced grade 1 cytokine release syndrome (CRS) on day 3, which resolved upon a single dose of the anti-interleukin-6 receptor monoclonal antibody tocilizumab. No neuro- or hematotoxicity were observed and, supported by a 100-day prophylaxis with letermovir, no CMV-reactivation occurred. BCMA-CAR T-cells expanded, cleared B cells in circulation and plasma cells in lymphoid tissue, reduced autoantibody levels, and re-induced stable drug-free remission with normalization of CK within three months.
Learning points for clinical practice: These data demonstrate that (i) a switch of CAR T-cell target can restore drug-free remission after relapse of AID after the first CAR T-cell treatment, (ii) repeated treatment with the same CAR T-cell product can be hampered by anti-CAR T-cells preventing engraftment and (iii) immunosuppressive effects of lymphodepletion are not effective to influence AID in the absence of CAR T-cell proliferation.
REFERENCES: [1] Müller F, Taubmann J, et al. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med . 2024; 390:687-700.
[2] Schett, G., Mackensen, A. & Mougiakakos, D. CAR T-cell therapy in autoimmune diseases. Lancet 402, 2034-2044 (2023).
Acknowledgements: NIL.
Disclosure of Interests: Andreas Wirsching: None declared, Fabian Müller Speakers Bureau: AstraZeneca, Abbvie, Beigene, BMS, Janssen, Kite/Gilead, Miltenyi, Novartis, Sobi, Taketa, Advisory Board: AstraZeneca, BMS, CRISPR Therapeutics, Janssen, Kite/Gilead, Miltenyi, Novartis, Sobi, Research Funding: MedImmune/AstraZeneca, Kite/Gilead, BMS, Melanie Hagen: None declared, Simon Völkl: None declared, Carlo Tur: None declared, Gabriella Raimondo: None declared, Jule Taubmann: None declared, Laura Bucci: None declared, Sascha Kretschmann: None declared, Michael Aigner Miltenyi (speaker honoraria), Miltenyi (consulting fees), Kyverna (research support), Markus Eckstein: None declared, Silvia Spörl: None declared, Soraya Kharboutli: None declared, Sebastian Boeltz: None declared, Armin Atzinger: None declared, Andreas Mackensen speaker honoraria: BMS, Century Therapeutics Celgene, Kyverna Gilead, Janssen, Miltenyi, and Novartis, consulting fees: BMS, Century Therapeutics Celgene, Kyverna Gilead, Janssen, Miltenyi, and Novartis, Georg Schett speaker honoraria: BMS, Cabaletta, Kyverna, Janssen, Miltenyi, and Novartis, Ricardo Grieshaber-Bouyer Kyverna (research support).
© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (