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 and NE were generally reversible. There was 1 Grade 5 AE of organizing pneumonia. Median CAR T cell levels measured by peak and area under the curve were 99 cells/µL (range, 0.4-2589) and 1542 cells/µL (range, 5.5-27239), respectively.

With ≥ 1 y follow-up, KTE-X19 demonstrated significant and durable clinical benefit, with a manageable safety profile in pts with R/R MCL for whom there are no curative treatment options.