Extended Follow-Up Shows Durable Outcomes, No New Safety Signals With Brexucabtagene Autoleucel in R/R B-ALL

Brexucabtagene autoleucel, a CAR T-cell therapy approved in 2021 for relapsed or refractory B-cell acute lymphoblastic leukemia, showed efficacious results and promising safety data at 2-year follow-up.

An extended follow-up of ZUMA-3 (NCT02614066) did not identify any new safety signals with brexucabtagene autoleucel (Tecartus) among patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). 1

“With longer follow-up and an expanded data set by independent review, outcomes remain durable in adults with relapsed or refractory [B-ALL]—most of whom were heavily pretreated, Bijal Shah, MD, MS, Moffitt Cancer Center said in a presentation of the findings. “Most patients benefited from [brexucabtagene autoleucel], regardless of age or baseline bone marrow blast percentage, with a lesser benefit observed in those with greater than 75% blasts.”

In October 2021, the FDA approved brexucabtagene autoleucel for patients with R/R B-ALL based on phase 1/2 findings from ZUMA-3, which demonstrated 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 complete response/complete response with incomplete blood count recovery (CR/CRi) rate of 70.9%, including a CR rate of 56.4%.2

During the 2022 ASCO Annual Meeting, Shah presented findings from the 2-year follow up. At a median follow-up time of 26.8 months (range, 20.7-32.6) for patients treated in phase 2 portion of the trial, and 29.7 months (range 20.7-58.3 months) for a pooled analysis of phase 1 and phase 2 patients, no new adverse events (AEs) of interest, including cytokine release syndrome, neurological events, or infections, were observed since the primary analysis. One new grade 5 AE occurred, graft-vs-host-disease, but it was determined not to be treatment related. A total of 4 deaths had occurred since the primary analysis, 1 from disease progression, 1 from COVID-19, and 2 following allogeneic stem cell transplant (alloSCT). The time of death for these 4 patients were day 564, 791, 554, and 667, respectively.1

Most participating patients had been heavily pretreated, with a median number of 2 therapies prior to study initiation. Nearly half the study population, (47%) had received upwards of 3 prior therapies before beginning brexucabtagene autoleucel.

Median overall survival (OS) for all treated patients was 25.4 months (95% CI, 16.2-not estimable [NE]) in both the phase 2 (n = 55) and pooled phase 1/2 analysis (n = 78). The CR/CRi rate per independent central review was 71% (56% CR rate) in the phase 2 treated population—these findings were consistent with the primary analysis.

Among patients with CR or CRi, the median OS was 26.0 months (95% CI, 21.9-NE) and 47.0 months (95% CI, 23.3-NE), for patients in the phase 2 portion of the trial and the pooled phase 1 portion of the trial, respectively. For patients who did not have CR or CRi, the median OS were 2.4 (95% CI, 0.7-NE) and 2.4 months (95% CI, 1.7-8.2), respectively. Of note, the median OS was not reached among patients with CR in the phase 2 cohort.

Moreover, at data cutoff, the median OS was not reached in patients between the age of 18 and 25 years nor among patients older than sixty years. Nor was it reached in patients with less than 5%, 25%-50%, or 50%-75% bone marrow blasts at baseline.

The median duration of response (DOR) for patients who proceeded with subsequent alloSCT was not reached (95% CI, 8.3-NE; n = 10). Twenty percent of patients proceeded to subsequent alloSCT, 8 of whom had CR, 2 had CRi, and 1 of whom had blast-free hypoplastic or aplastic bone marrow. The median OS in this population was not reached (95% CI, 8.3-NE; n = 11).

In total, 39 patients responded to treatment. Among these, 6 were in ongoing remission without receiving subsequent stem cell transplant or anti-cancer therapy at the data cutoff. Six had required subsequent anti-cancer therapy, 4 of these patients were in remission and 2 had passed away at data cutoff. Ten patients progressed to subsequent alloSCT; 6 of these patients were in remission, 3 had died, and had relapsed at data cutoff. Besides these patients, there were 14 additional relapses and 3 deaths at 26.8 months of median follow-up.

Of note, at the time of data cutoff, none of the patients who had responded to treatment had evidence of CAR T cells detectable in their system. This finding suggests that “persistence of functional CAR T cells in the blood is not required for a durable response,” Shah said.


  1. Shah BD, Ghobadi A, Oluwole OO, et al. Two-year follow-up with KTE-X19, an anti-CD19 chimeric antigen receptor T-cell therapy, in adult patients with relapsed/refractory b-cell acute lymphoblastic leukemia in ZUMA-3. J Clin Oncol. 2022;40(suppl 16):7010. doi:10.1200/JCO.2022.40.16_suppl.7010
  2. 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. October 1, 2021. Accessed July 14, 2022. https://bwnews.pr/3iq0Chg