journal contribution
posted on 2023-04-04, 00:43 authored by Sarah M. Larson, Christopher M. Walthers, Brenda Ji, Sanaz N. Ghafouri, Jacob Naparstek, Jacqueline Trent, Jia Ming Chen, Mobina Roshandell, Caitlin Harris, Mobina Khericha, Thomas Schweppe, Beata Berent-Maoz, Stanley B. Gosliner, Amr Almaktari, Melanie Ayala Ceja, Martin S. Allen-Auerbach, Jonathan Said, Karla Nawaly, Monica Mead, Sven de Vos, Patricia A. Young, Caspian Oliai, Gary J. Schiller, John M. Timmerman, Antoni Ribas, Yvonne Y. Chen CD14/CD20 depletion did not significantly alter regulatory T (Treg) cell content in CART19/20 cell product and in patient peripheral blood post infusion. Intracellular staining of starting (unactivated) TN/MEM population, CART19/20 final product, and patient PBMC collected 14 days post CART19/20 infusion. FOXP3+ frequency is shown as a percentage of CD3+CD4+ T cells.
Funding
Parker Institute for Cancer Immunotherapy (Parker Institute)
Jean and Stephan Kaplan
Aramont Clinical/Translational Research Program in Hematologic Malignancies
Hornsey Foundation
Office of Extramural Research, National Institutes of Health (OER)
Jaime Erin Follicular Lymphoma Research Consortium
History
ARTICLE ABSTRACT
To address antigen escape and loss of T-cell functionality, we report a phase I clinical trial (NCT04007029) evaluating autologous naive and memory T (TN/MEM) cells engineered to express a bispecific anti-CD19/CD20 chimeric antigen receptor (CAR; CART19/20) for patients with relapsed/refractory non-Hodgkin lymphoma (NHL), with safety as the primary endpoint. Ten patients were treated with 36 × 106 to 165 × 106 CART19/20 cells. No patient experienced neurotoxicity of any grade or over grade 1 cytokine release syndrome. One case of dose-limiting toxicity (persistent cytopenia) was observed. Nine of 10 patients achieved objective response [90% overall response rate (ORR)], with seven achieving complete remission [70% complete responses (CR) rate]. One patient relapsed after 18 months in CR but returned to CR after receiving a second dose of CART19/20 cells. Median progression-free survival was 18 months and median overall survival was not reached with a 17-month median follow-up. In conclusion, CART19/20 TN/MEM cells are safe and effective in patients with relapsed/refractory NHL, with durable responses achieved at low dosage levels.
Autologous CD19/CD20 bispecific CAR-T cell therapy generated from TN/MEM cells for patients with NHL is safe (no neurotoxicity, maximum grade 1 cytokine release syndrome) and demonstrates strong efficacy (90% ORR, 70% CR rate) in a first-in-human, phase I dose-escalation trial.This article is highlighted in the In This Issue feature, p. 517
