CD19 CAR T-cell therapy is feasible for patients with pemphigus vulgaris treated without lymphodepletion in the RESET-PV trial
Abstract
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.
Article Details
Authors (33)
Daniel Nunez
1Cabaletta Bio, Philadelphia, PA
Jason Stadanlick
1Cabaletta Bio, Philadelphia, PA
Thomas Furmanak
1Cabaletta Bio, Philadelphia, PA
Jessica Goldenberg
1Cabaletta Bio, Philadelphia, PA
Gaurav S. Choudhary
Larissa Ishikawa
1Cabaletta Bio, Philadelphia, PA
Mallorie Werner
1Cabaletta Bio, Philadelphia, PA
Zachary Vorndran
1Cabaletta Bio, Philadelphia, PA
Fatemeh Hadi-Nezhad
1Cabaletta Bio, Philadelphia, PA
Daniel Thompson
1Cabaletta Bio, Philadelphia, PA
Domenick Braccia
1Cabaletta Bio, Philadelphia, PA
Alexandra Ellis
1Cabaletta Bio, Philadelphia, PA
Justin Cicarelli
1Cabaletta Bio, Philadelphia, PA
Steve Flanagan
1Cabaletta Bio, Philadelphia, PA
Jazmean Williams
1Cabaletta Bio, Philadelphia, PA
Danielle Kobulsky
1Cabaletta Bio, Philadelphia, PA
Amanda Toreki
1Cabaletta Bio, Philadelphia, PA
Candice Schreiber
1Cabaletta Bio, Philadelphia, PA
Naomi Bass
1Cabaletta Bio, Philadelphia, PA
Angelina Impagliazzo
1Cabaletta Bio, Philadelphia, PA
Quynh Lam
1Cabaletta Bio, Philadelphia, PA
Arturo Dominguez
2Department of Dermatology, University of Texas Southwestern, Dallas, TX
Farrukh Awan
3Department of Hematology/Oncology, University of Texas Southwestern, Dallas, TX
Xiaolong Zhou
Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University
Joaquin Brieva
4Department of Dermatology, Northwestern University, Chicago, IL
Mehrdad Abedi
5Division of Malignant Hematology/Cellular Therapy and Transplantation, University of California, Davis, Davis, CA
Emanual Maverakis
Kiren Kresa-Reahl
1Cabaletta Bio, Philadelphia, PA
Raj Tummala
1Cabaletta Bio, Philadelphia, PA
David Chang
Gwendolyn K. Binder
1Cabaletta Bio, Philadelphia, PA
Jenell Volkov
1Cabaletta Bio, Philadelphia, PA
Samik Basu
1Cabaletta Bio, Philadelphia, PA