Bispecific T cell engagers for treatment-refractory autoimmune connective tissue diseases
Christina Düsing, Andrea-Hermina Györfi, Ayla Nadja Stütz, Laura-Marie Lahu, Franca Sophie Deicher, Y. LI, Peter‐Martin Bruch, Alexandru-Emil Matei, A. Micu, Tim Filla, Sarah Koziel, Alexander Sebastian Hölscher, Manuel Röhrich, Hanns-Martin Lorenz, Mareike Cramer, Gerald Antoch, Jörg Timm, Yousef Abusabha, Tobias Ruck, Bernhard Homey, Alexander Kreuter, Björn Buehring, Aleksandar Radujkovic, Claus Peter Heußel, Melanie Hagen, Ricardo Grieshaber-Bouyer, Georg Schett, A. Brunn, Sascha Dietrich, Wolfgang Merkt, Jörg H. W. Distler
Abstract
Autoimmune-mediated connective tissue diseases such as antisynthetase syndrome (ASyS) and systemic sclerosis (SSc) have a high unmet medical need. Here we report on treatment under compassionate use with the CD19×CD3 T cell engager (TCE) blinatumomab and the BCMA×CD3 TCE teclistamab in five patients with treatment-refractory ASyS and in five patients with treatment-refractory SSc, respectively. Induction therapy with blinatumomab or teclistamab reduced target cells in affected muscle and skin, respectively, and decreased autoantibody titers. Blinatumomab induced rapid clinical, serological and histological improvement of myositis and stabilization of interstitial lung disease (ILD) in patients with ASyS. Teclistamab improved skin fibrosis, stabilized ILD and resolved tendon friction rubs in patients with SSc. Inhibition of B cell redifferentiation by maintenance therapy with rituximab (RTX) enabled prolonged disease control, even for patients previously unresponsive to RTX. Treatment was associated with adverse events including cytokine release syndrome (CRS) up to grade 3, in two patients with ASyS and in all patients with SSc. No immune effector cell-associated neurotoxicity syndrome (ICANS) occurred. Respiratory infections treated with antibiotics occurred in six patients. Blinatumomab and teclistamab may offer potential as rescue therapies for patients with treatment-refractory ASyS and SSc.