Enhanced CAR T-Cell Therapy for Lymphoma after Previous Failure
Jakub Svoboda, Daniel J. Landsburg, James N. Gerson, Sunita D. Nasta, Stefan K. Barta, Elise A. Chong, Michael Cook, Noelle V. Frey, Joanne Shea, Amanda Cervini, Amy Marshall, Megan Four, Megan M. Davis, Julie K. Jadlowsky, Anne Chew, Edward Pequignot, Vanessa Gonzalez, Julia Han Noll, Luca Paruzzo, Juliana Rojas-Levine, Gabriela Plesa, John Scholler, Don L. Siegel, Bruce L. Levine, David L. Porter, Saba Ghassemi, Marco Ruella, Andrew J. Rech, Rachel Leskowitz, Joseph A. Fraietta, Wei‐Ting Hwang, Elizabeth O. Hexner, Stephen J. Schuster, Carl H. June
Abstract
BACKGROUND: Chimeric antigen receptor (CAR) T cells targeting CD19 have transformed the treatment of B-cell cancers, but many patients do not have long-term remission. We designed an anti-CD19 enhanced (armored) CAR T-cell product (huCART19-IL18) that secretes interleukin-18 to enhance antitumor activity. METHODS: . RESULTS: A total of 21 patients received huCART19-IL18. Cytokine release syndrome occurred in 62% of the patients (47% with grade 1 or 2), and immune effector-cell-associated neurotoxicity syndrome occurred in 14% (all grade 1 or 2). No unexpected adverse events were observed. Robust CAR T-cell expansion was detected across all dose levels. At 3 months after infusion, a complete or partial response was seen in 81% of the patients (90% confidence interval [CI], 62 to 93) and a complete response in 52% (90% CI, 33 to 71). With a median follow-up of 17.5 months (range, 3 to 34), the median duration of response was 9.6 months (90% CI, 5.5 to not reached). CONCLUSIONS: In this small study, huCART19-IL18 had a safety profile consistent with other CAR T-cell treatments and showed promising efficacy at low cell doses in patients with lymphoma after the failure of previous anti-CD19 CAR T-cell therapy. (ClinicalTrials.gov number, NCT04684563.).