As reported in The Lancet by Shah et al, the pivotal phase II ZUMA-3 trial has shown a high rate of complete remission with the autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy brexucabtagene autoleucel (formerly KTE-X19) in adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

Study Details

A total of 71 patients from sites in the United States, Canada, and Europe were enrolled in the trial; they underwent leukapheresis between October 2018 and October 2019. Patients received a single brexucabtagene autoleucel infusion at 1 × 10⁶ CAR T cells/kg following leukapheresis and conditioning chemotherapy with fludarabine (25 mg/m² on days −4, −3, and −2) and cyclophosphamide (900 mg/m² on day −2). The primary endpoint was the rate of overall complete remission or complete remission with incomplete hematologic recovery on central assessment. Efficacy and safety analyses were performed in the treated population, consisting of all patients who received a dose of brexucabtagene autoleucel.

Responses

Among the 71 patients undergoing leukapheresis, brexucabtagene autoleucel was successfully manufactured for 65 patients (92%) and administered to 55 patients (77%).

At a median follow-up of 16.4 months (interquartile range = 13.8–19.6 months), complete remission or complete remission with incomplete hematologic recovery occurred in 39 patients (71%, 95% confidence interval [CI] = 57%–82%, P < .0001 vs historical control rate of ≤ 40%), with complete remission occurring in 31 patients (56%). Allogeneic stem cell transplantation consolidation was performed in 10 patients (18%) after treatment with brexucabtagene autoleucel. The median duration of remission was 12.8 months (95% CI = 8.7 months to not estimable). Measurable residual disease negativity was achieved in 42 patients (76%; P < .0001 vs historical control rate of 30%) and in 38 responders (97%).

Median overall survival among responders was not reached. Among all treated patients, median relapse-free survival was 11.6 months (95% CI = 2.7–15.5 months), and median overall survival was 18.2 months (95% CI = 15.9 months to not estimable).

Adverse Events

Grade ≥ 3 adverse events occurred in 95% of treated patients, with the most common being anemia (49%) and pyrexia (36%). Any-grade cytokine-release syndrome occurred in 89% of patients and was grade ≥ 3 in 24%. Any-grade neurologic toxicity occurred in 60% and was grade ≥ 3 in 25%. Grade ≥ 3 infections occurred in 25%. Adverse events led to death in 10 patients (18%); death was considered related to treatment in 2 patents, due to brain herniation in 1 and septic shock in 1.

The investigators concluded: “KTE-X19 [brexucabtagene autoleucel] showed a high rate of complete remission or complete remission with incomplete haematological recovery in adult patients with relapsed or refractory B-precursor ALL, with the median overall survival not reached in responding patients, and a manageable safety profile. These findings indicate that KTE-X19 has the potential to confer long-term clinical benefit to these patients.”

Bijal D. Shah, MD, of the Moffitt Cancer Center, is the corresponding author of The Lancet article.

Disclosure: The study was funded by Kite, a Gilead Company. For full disclosures of the study authors, visit thelancet.com.