BCMA CAR T cells in a patient with relapsing idiopathic inflammatory myositis after initial and repeat therapy with CD19 CAR T cells
Fabian Müller, Andreas Wirsching, Melanie Hagen, Simon Völkl, Carlo Tur, Maria Gabriella Raimondo, Jule Taubmann, Laura Bucci, Liang Zhang, Sascha Kretschmann, Michael Aigner, Markus Eckstein, Silvia Spörl, Soraya Kharboutli, Sebastian Boeltz, Armin Atzinger, Luis E. Muñoz, Georg Schett, Andréas Mackensen, Ricardo Grieshaber‐Bouyer
Abstract
CD19 chimeric antigen receptor (CD19 CAR) T cell therapy has been shown to induce stable drug-free remission in patients with refractory autoimmune disease. The management of potential relapses is currently unclear. Here we report on a 45-year-old woman with treatment-refractory Jo-1-associated anti-synthetase syndrome, who initially achieved disease remission after CD19 CAR T cell therapy but then experienced disease relapse after 9 months. After reinfusion of the same product, CAR T cells failed to expand and T cells targeting the CD19 CAR were detected. Despite full-dose lymphodepletion, no clinical response was observed. After bridging with anti-CD38 antibody daratumumab, which was efficacious with limited durability, plasma-cell-targeting B-cell maturation antigen (BCMA) CAR T cell therapy was performed. BCMA CAR T cells expanded, cleared plasma cells in lymphoid tissue, reduced autoantibody levels and re-induced stable drug-free remission. This case highlights the challenges in CAR T cell reinfusion, the potential of alternative targets and products, and suggests that the depletion of plasma cells may enhance therapeutic outcomes in patients who become treatment-refractory.