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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. [ABSTRACT FROM AUTHOR]

Background Although ∼1/2 of adult patients (pts) with acute lymphoblastic leukemia (ALL) achieve long-term survival, those who relapse have poor long-term outcomes. The initial report of Phase (P) 1 of ZUMA-3, the P1/2 trial of KTE-X19 for treatment of relapsed/refractory (R/R) ALL (NCT02614066), demonstrated a 71% complete remission (CR) rate (CR or CR with incomplete hematologic recovery [CRi]), 88% undetectable minimal residual disease (MRD), and manageable toxicity (Shah et al. ASH 2017. #888). Here, we present updated ZUMA-3 P1 safety and efficacy data. Methods Adult pts (≥ 18 y) with R/R ALL (Ph+ allowed), > 5% bone marrow (BM) blasts, and ECOG 0-1 received 2, 1, or 0.5 × 106 CAR T cells/kg after low-dose conditioning chemotherapy. The primary endpoint for P1 was incidence of dose-limiting toxicities (DLTs). Key secondary endpoints included incidence and time to onset and resolution of adverse events (AEs), rate of undetectable MRD remission in the BM, and duration of remission. Safety analyses included all pts who received KTE-X19; pts with ≥ 2 months of follow-up were evaluated for efficacy. Results As of April 12, 2018, 35 pts have received KTE-X19 (median follow-up of 11 months [range, 2 −25 months]). Median age was 40 years (range, 18 – 69 years), 51% male, 66% ECOG 1, 37% prior blinatumomab, and 60% ≥ 3 prior lines of treatment. Median BM blast burden at Screening was 70% (range, 5 −100). Six, 14, and 15 pts received 2, 1, and 0.5 × 106 cells/kg doses, respectively. No DLTs were observed in the DLT period. The most common Grade ≥ 3 AEs were hypotension (40%) pyrexia (34%), decreased platelet counts (34%), and anemia (31%). Grade ≥ 3 cytokine release syndrome (CRS) occurred in 9 pts (26%, median time to onset 5 days [range, 1 −15 days]); events resolved in all pts (excluding 2 with a Grade 5 event), and the median time to resolution was 11 days (range, 7 −42 days). There were 2 KTE-X19-related Grade 5 events: 1 cerebral infarction at the 0.5 × 106 cells/kg dose and 1 previously reported multiorgan failure secondary to CRS at the 2 × 106 cells/kg dose. Grade ≥ 3 neurologic events occurred in 16 pts (46%, median time to onset 7 days [range, 4 −24 days]); neurologic events resolved in all pts (excluding 2 patients with unresolved events at death), with a median time to resolution of 17 days (range, 6 −53 days). Among the 32 pts evaluable for response, the overall rate of undetectable MRD was 78% (95% CI, 60%–91%).CR or CRi was achieved by 23 pts (72%), and 1 pt (3%) had blast-free BM. Conclusion High remission rates were achieved by adult pts with R/R ALL, with ∼3/4 of pts achieving CR or CRi with undetectable MRD after a single dose of KTE-X19 in ZUMA-3. The safety profile was generally manageable, and most cases of high-grade CRS and neurologic events resolved. These results demonstrate that KTE-X19 offers clinical benefit for pts with otherwise limited treatment options. [ABSTRACT FROM AUTHOR]