Daniel Nunez, Jason Stadanlick, Thomas Furmanak, Jessica Goldenberg, Gaurav S. Choudhary, Larissa Ishikawa, Mallorie Werner, Zachary Vorndran, Fatemeh Hadi-Nezhad, Daniel Thompson, Domenick James Braccia, Alexandra Ellis, Justin Cicarelli, Steve Flanagan, Jazmean Williams, Danielle Rose Kobulsky, Amanda Toreki, Candice Schreiber, Naomi Bass, Angelina Impagliazzo, Quynh Lam, Arturo R. Domínguez, Farrukh T. Awan, Xiaolong Alan Zhou, Joaquin Carlos Brieva, Mehrdad Abedi, Emanual Maverakis, Kiren Kresa-Reahl, Raj Tummala, David J Chang, Gwendolyn Knowlton Binder, Jenell Volkov, Samik Basu
ABSTRACT: Lymphodepleting preconditioning (LD) is essential for the efficacy of chimeric antigen receptor (CAR) T-cell therapy in hematologic malignancies. However, in the setting of autoimmune diseases (ADs), the contribution of LD for efficacy is unclear. Here, we report on the early safety, efficacy, and correlative data of the first 4 patients with pemphigus vulgaris (PV) who received resecabtagene autoleucel (rese-cel), a fully human CD19 CAR T-cell therapy, without LD in the RESET-PV trial, a substudy of the DesCAARTes trial. Following infusion, pemphigus disease area index scores improved significantly in all patients. A favorable safety profile was observed, with a single episode of grade 1 cytokine release syndrome. Immune effector cell-associated neurotoxicity was not observed. Rese-cel expansion was similar in patients with PV compared with other rese-cel-treated patients with AD who received LD. B-cell depletion was observed in all patients with PV, with 3 of 4 patients achieving B-cell aplasia. Elevations in serum B-cell activating factor (BAFF) level were observed, with 3 of 4 patients achieving levels within the lowest end of the range exhibited in rese-cel-treated patients with AD who received LD. PV autoantibodies decreased in 2 of 4 patients. These preliminary data suggest that LD may be dispensable for humanized CAR T-cell efficacy in patients with AD. This trial was registered at www.clinicaltrials.gov as NCT04422912.