KTE-X19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy, in Patients (Pts) with Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL): Results of the Phase 2 ZUMA-2 Study

• Published in: Biology of blood and marrow transplantation 2020-03, Vol.26 (3), p.S1-S1
• Main Authors: Wang, Michael, Munoz, Javier, Goy, Andre, Locke, Frederick L., Jacobson, Caron A., Hill, Brian T., Timmerman, John M., Holmes, Houston, Jaglowski, Samantha, Flinn, Ian W., McSweeney, Peter A., Miklos, David B., Pagel, John M., Kersten, Marie José, Peng, Weimin, Zheng, Lianqing, Rossi, John M., Jain, Rajul K., Rao, Arati V., Reagan, Patrick M.
• Format: Article
• Language: English
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2019.12.135

Outcomes with salvage regimens in pts with MCL who progress after Bruton tyrosine kinase inhibitor (BTKi) therapy are poor. ZUMA-2 is a Phase 2, registrational, multicenter study evaluating KTE-X19, an autologous anti-CD19 CAR T cell therapy, in pts with R/R MCL (1-5 therapies, including a BTKi). We present interim efficacy and safety results. Evaluate efficacy and safety of KTE-X19 in R/R MCL. Eligible pts (≥ 18 y) with R/R MCL had an ECOG of 0-1 and ≤ 5 prior therapies, including chemotherapy, an anti-CD20 antibody, and a BTKi. Pts underwent leukapheresis and conditioning chemotherapy followed by KTE-X19 infusion at 2 × 106 cells/kg. Bridging therapy with dexamethasone, ibrutinib, or acalabrutinib was permitted. The primary endpoint was objective response rate (ORR; complete response [CR] + partial response) assessed by an Independent Review Committee per the Lugano Classification (Cheson, et al. J Clin Oncol. 2014). Interim efficacy endpoints were investigator-assessed using the revised IWG Response Criteria for Malignant Lymphoma (Cheson, et al. J Clin Oncol. 2007). Key secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), frequency of adverse events (AEs), and blood levels of CAR T cells and cytokines. Sixty pts received KTE-X19; here, we present results in pts with ≥ 1 y follow-up. Updated results in all 60 pts will be reported in the presentation. As of May 30, 2018, 28 pts received KTE-X19 with ≥ 1 y follow-up (median, 13.2 mo). The median age was 65 y; 43% of pts had an ECOG score of 1; 21% had blastoid morphology; 82% had stage IV disease; 50% had intermediate/high-risk MIPI; and 86% received a median of 4 prior therapies. In 20 of 28 pts with available data, the median Ki-67 index was 38%. Eight pts received bridging therapy; all had disease present post-bridging. Investigator-assessed ORR was 86% (95% CI, 67-96) with a CR rate of 57% (95% CI, 37-76). As of May 30, 2018, 75% of responders remained in response, and 64% of treated pts had ongoing responses. The 12-month rates of DOR, PFS, and OS were 83% (95% CI, 60-93), 71% (95% CI, 50-84), and 86% (95% CI, 66-94), respectively; medians were not reached. The most common Grade ≥ 3 AEs were anemia (54%), platelet count decreased (39%), and neutropenia (36%). Grade 3/4 cytokine release syndrome (CRS) assessed by Lee et al. (Blood. 2014) and Grade 3/4 neurologic events (NE) occurred in 18% and 46% of pts, respectively, with no Grade 5 events. CRS