Background: Relapsed or refractory B-precursor acute lymphoblastic leukemia (R/R B-ALL) in adults is associated with an unfavorable prognosis. Brexucabtagene autoleucel (KTE-X19) is an autologous anti-CD19 CAR T-cell therapy that has been approved by the US FDA for the treatment of adult patients with R/R B-ALL, based on the results of ZUMA-3 trial. However, the efficacy and safety of KTE-X19 for the treatment of R/R B-ALL in the Chinese population have not been explored. We conducted a single-arm, multi-center, phase II trial (ChiCTR2300073872) to evaluate the efficacy and safety of KTE-X19 in Chinese population with R/R B-ALL, with this report presenting updated outcomes after >6 months median follow-up.

Methods: Eligible patients were aged 18 years or older, with Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, and morphological disease in the bone marrow (>5% blasts). After leukapheresis and conditioning chemotherapy, patients received a single infusion of KTE-X19 (1 × 10⁶ CAR T cells/kg). The primary endpoint was the overall complete remission (OCR) rate (complete remission [CR] + CR with incomplete hematologic recovery [CRi]) by central assessment. Secondary endpoints included duration of remission (DOR), relapse-free survival (RFS), overall survival (OS), minimal residual disease (MRD) negativity rate, and allogeneic stem cell transplantation (allo-SCT) rate.

Results: As of the data cutoff (February 13, 2025), 32 patients had been enrolled and 28 patients received KTE-X19 treatment. The median age of treated patients was 36 years (range 19-66). The median bone marrow blast percentage at baseline was 31.25% (range 0-98%). One patient (3.6%) aged 65 years or older. 61% of patients had ECOG PS of 1. Ten patients (35.7%) had Philadelphia chromosome-positive (Ph+) disease. One patient (3.6%) had CNS-2 disease. One patient (3.6%) had extramedullary disease at screening. Patients had a median of 2 (range 1-5) prior lines of therapy; one patient (3.6%) previously received blinatumomab, four patients (14.3%) previously received inotuzumab ozogamicin, and seven patients (25%) previously received allo-SCT.

Median follow-up time for this analysis was 10.3 months (90% CI 5.9, 9.1). Among 28 patients received KTE-X19 treatment, the best OCR rate was 78.6% (90% CI 62.0%, 90.2%) and the best CR rate was 67.9%. The median time to first response was 1 month. All responders had MRD negativity. Nine patients (32.1%) underwent allo-SCT after KTE-X19 infusion. Median RFS, median DOR and median OS were not reached. The estimated 1-year RFS rate was 60.4% and 1-year DOR rate was 76.9%. Among the patients with CR/CRi , the median time to peak CAR T-cell levels in blood post-KTE-X19 was 14 days (range 7-14) and the median peak CAR T-cell levels in blood was 47.64 cells/μL(range 5.13-2725.83). The median area under the curve from Days 0-28 of CAR T-cell levels was 492.98 cell/μL×days (range 81.70-13515.45).

No new safety signals were observed in the Chinese population. The most common treatment-emergent adverse events of grade 3 or higher were decreased platelet count (21 [75%] patients), decreased white blood cell count (21 [75%] patients), pyrexia (20 [71.4%]), decreased lymphocyte count (19 [67.9%]) and decreased neutrophil count (19 [67.9%]). Cytokine release syndrome (CRS) of any grade occurred in 26 patients (92.9%), with 6 patients (21.4%) experiencing grade≥3 CRS. Neurological events (NEs) of any grade occurred in 10 patients (35.7%), with 4 patients (14.3%) experiencing grade≥3 NEs. No grade 5 CRS or NEs occurred.

Conclusions: After >6 months median follow-up, KTE-X19 demonstrated a high rate of OCR in Chinese adult patients with R/R B-ALL, with median RFS, DOR and OS not reached, and a manageable safety profile. These findings support its therapeutic potential and clinical benefit in the Chinese population.

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2025
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