FDA Approves Brexucabtagene Autoleucel for Relapsed/Refractory B-ALL


The FDA has approved brexucabtagene autoleucel as a treatment for adult patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia.



The FDA has approved brexucabtagene autoleucel (Tecartus; formerly KTE-X19) as a treatment for adult patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (B-ALL).1

The regulatory decision was based on findings from the phase 1/2 ZUMA-3 study (NCT02614066), which showed that at a median follow-up of 16.4 months (range, 10.3-22.1), a single infusion of the CAR T-cell therapy elicited a high and durable response rate in heavily pretreated patients with relapsed/refractory B-ALL, the majority of whom had a high disease burden.2

Specifically, data from the phase 2 portion of the trial presented during the 2021 ASCO Annual Meeting showed that brexucabtagene autoleucel elicited a complete response/complete response with incomplete blood count recovery (CR/CRi) rate of 70.9%, which included a CR rate of 56.4%.

The international, multicenter, phase 1/2 trial enrolled patients with relapsed/refractory B-ALL and bone marrow blasts that were greater than 5% who were at least 18 years of age. Notably, patients were not able to have previously received blinatumomab (Blincyto).

Earlier results from the phase 1 portion of the research showed that brexucabtagene autoleucel had a manageable toxicity profile with an overall CR/CRi rate of 83%. The recommended phase 2 dose of the CAR T-cell product was determined to be 1 x 106 CAR T cells/kg.3

Seventy-one adult patients were enrolled to the phase 2 portion of the trial and they received conditioning chemotherapy comprised of fludarabine 25 mg/m2 on days -4, -3, and -2, as well as cyclophosphamide at 900 mg/m2 on day -2. A single infusion of the CAR T-cell therapy was administered on day 0 at a dose of 1 x 106 anti-CD19 CAR T cells/kg.

The primary end point of the trial was CR/CRi rate by central assessment, and key secondary end points included minimal residual disease (MRD) negativity rate, duration of response (DOR), relapse-free survival (RFS), overall survival, safety, and CAR T-cell levels in the blood and cytokine levels in serum.

Of the 71 patients enrolled to the trial, 14 patients did not receive treatment because of toxicities (n = 7), eligibility criteria were not met (n = 3), product was not available (n = 1), patient consent was withdrawn (n = 1), or for other reasons not specified (n = 2). A total of 57 patients were given conditioning chemotherapy; 2 of these patients did not receive treatment after this, which left 55 patients who received the CAR T-cell therapy.

Among the study participants, the median age was 40 years (range, 19-84), and the majority were male (60%) with an ECOG performance status of 1 (71%). Additionally, 27% of patients had Philadelphia chromosome positivity and all had central nervous system disease at baseline. Patients received a median of 2 prior therapies (range, 1-8) and 47% of patients had undergone 3 or more prior lines of treatment.

The majority of patients has relapsed on, or were refractory to, 2 or more prior systemic lines of treatment (78%); 45% of patients had received prior treatment with blinatumomab, 22% previously received inotuzumab ozogamicin (Besponsa), and 42% had undergone prior autologous stem cell transplant (ASCT). Moreover, the median rate of bone marrow blasts at screening was 65% (range, 5%-100%), and the median rate at preconditioning after bridging chemotherapy was 59% (range, 0%-98%).

Moreover, the median time to initial CR/CRi was 1.1 months (range, 0.85-2.99). In responders, the MRD negativity rate with the CAR T-cell therapy was 97%, with a sample unavailable for 1 patient. Eighteen percent of patients received ASCT at a median of 98 days (range, 60-207) after having received the CAR T product.

The median DOR was 12.8 months, with or without censoring patients at subsequent ASCT. As of data cutoff, 31% of the patients who achieved a CR or CRi experienced ongoing remissions without receiving subsequent ASCT. Additionally, the median RFS was 11.6 months and 14.2 months for those who achieved a CR/CRi.

Regarding safety, the most common grade 3 or higher adverse effects (AEs) included anemia (49%) and pyrexia (36%). Ten cases of grade 5 AEs were reported, 4 of which were ALL; 2 were treatment-emergent from the CAR T-cell product and included brain herniation and septic shock; 3 occurred after initiation of another cancer treatment and included fungal pneumonia, sepsis, and respiratory failure; and 1 was pneumonia unrelated to treatment with brexucabtagene autoleucel.

No grade 5 cytokine release syndrome (CRS) or other neurological AEs were reported. However, 24% of patients experienced grade 3 or higher CRS and 25% reported other grade 3 or higher neurological events. To treat these AEs, patients were given tocilizumab (Actemra; 80%), steroids (75%), and vasopressors (40%).


  1. U.S. FDA Approves Kite’s Tecartus® as the First and Only Car T for Adults With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia. Kite. News release. Published October 1, 2021. Accessed October 1, 2021. https://bwnews.pr/3iq0Chg.
  2. Shah B, Ghobadi A, Oluwole O, et al. Phase 2 results of the ZUMA-3 study evaluating KTE-X19, an anti-CD19 chimeric antigen receptor T-cell therapy, in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia. J Clin Oncol. 2021;39(15):7002-7002. doi:10.1200/JCO.2021.39.15_suppl.7002
  3. Shah BD, Bishop MR, Oluwole OO, et al. End of phase I results of ZUMA-3, a phase 1/2 study of KTE-X19, anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in adult patients (pts) with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). J Clin Oncol. 2019;37(suppl; abstr 70060). doi:10.1200/JCO.2019.37.15_suppl.7006
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