PS962 PHASE 1 RESULTS OF ZUMA‐4: KTE‐X19, AN ANTI‐CD19 CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY, IN PEDIATRIC AND ADOLESCENT PATIENTS WITH RELAPSED/REFRACTORY B CELL ACUTE LYMPHOBLASTIC LEUKEMIA
Bibliographic record
Abstract
Please indicate where the abstract has been published before: This abstract has also been submitted to ASPHO 2019 Background: KTE‐X19, formerly KTE‐C19, is an autologous anti‐CD19 chimeric antigen receptor T cell therapy. Early clinical experience with KTE‐X19 in children and adolescents with relapsed/refractory B cell acute lymphoblastic leukemia is promising. Here, we present end of Phase 1 results from ZUMA‐4. Aims: Evaluate the safety and efficacy of KTE‐X19 in pediatric and adolescent patients with relapsed/refractory B cell acute lymphoblastic leukemia. Methods: In this dose‐finding study, patients aged 2–21 years with relapsed/refractory B cell acute lymphoblastic leukemia (Philadelphia chromosome‐positive allowed) and > 5% bone marrow blasts received either 2 or 1 × 10 6 chimeric antigen receptor T cells/kg following conditioning chemotherapy. The primary endpoint was incidence of dose‐limiting toxicities. Secondary endpoints included complete remission (CR) rate (CR and CR with incomplete hematologic recovery [CR + CRi]) and overall survival. KTE‐X19 formulation was optimized in a second 1 × 10 6 dose group using a lower infusion volume (40‐mL versus 68‐mL). Results: As of October 11, 2018, 24 patients received KTE‐X19 (median age of 13 years [range, 3–20 years]; 42% ≥ 3 prior regimens; 29% primary refractory disease; 25% relapsed/refractory post‐allogeneic stem cell transplantation; 37% [range, 0%–100%], median preconditioning bone marrow blast count). The median follow‐up was 13.2 months. Four patients received a targeted 2 × 10 6 cells/kg with no dose limiting toxicities in evaluable patients (n = 3). Patients were then enrolled at a targeted 1 × 10 6 cells/kg to improve the overall safety profile: 11 received the 68‐mL formulation, and 9 received the 40‐mL. Overall, the most common Grade ≥ 3 adverse events were hypotension (50%) and anemia (33%). Rates of Grade ≥ 3 neurologic events were 25%, 36%, and 11% in the 2 × 10 6 , 1 × 10 6 (68‐mL), and 1 × 10 6 (40‐mL) groups, respectively, and rates of Grade ≥ 3 cytokine release syndrome were 75%, 18%, and 22%. Overall, there were 3 Grade 5 adverse events that were unrelated to KTE‐X19. All but 2 patients in the 40‐mL, 1 × 10 6 group were evaluable for efficacy with ≥ 2 months of follow‐up. The CR + CRi rate was 100%, 64%, and 71% in the 2 × 10 6 , 1 × 10 6 (68‐mL), and 1 × 10 6 (40‐mL) groups, respectively, with 25%, 71%, and 100% of CR + CRi patients in ongoing response as of the data cutoff; and 75%, 73%, and 86% of all patients had undetectable minimal residual disease. Median overall survival was not reached for either 1 × 10 6 group and was 8 months for the 2 × 10 6 group. Chimeric antigen receptor T cell expansion was observed in all dose/formulation groups. Summary/Conclusion: Children and adolescents with relapsed/refractory B cell acute lymphoblastic leukemia achieved high minimal residual disease‐negative remission rates with a manageable safety profile and promising efficacy after a single dose of KTE‐X19. Phase 2 of ZUMA‐4 is ongoing at the 40‐mL, 1 × 10 6 cells/kg dose.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".