Brexucabtagene Autoleucel Shows High Rate of Durable Response at 3 Years

Three-year follow-up results of chimeric antigen receptor (CAR) T-cell therapy brexucabtagene autoleucel (Tecartus) in adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) demonstrated high rates of durable response and a median overall survival of 26 months, according to results released Thursday.

The rate of complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) was 71% and the CR rate was 56%, according to a statement. Results came from the pivotal ZUMA-3 study; the findings were presented during a poster session at the 5th European CAR T-cell Meeting in Rotterdam, the Netherlands, according to drug manufacturer Kite.

The safety profile was found to be consistent since the 2-year analysis.

The FDA approved brexucabtagene autoleucel for adult patients diagnosed with R/R B-ALL in October 2021.

“For adult patients living with ALL, there is a need for therapeutic options that provide long-term responses,” Bijal Shah, MD, ZUMA-3 investigator and medical oncologist at the Moffitt Cancer Center in Tampa, Florida, said in a statement. “The continued durable response and significant improvement in survival indicated by these new data can potentially establish a new standard of care for adult patients living with this aggressive form of leukemia.”

ZUMA-3 is an ongoing phase 1/2 study of brexucabtagene autoleucel in adult patients with ALL whose disease is refractory to or has relapsed following standard systemic therapy or hematopoietic stem cell transplantation.

In the phase 2 treated patient cohort (n = 55), the median follow-up was 38.8 months (range, 32.7-44.6). The OS rate at 36.0 months was 47.1% (95% CI, 32.7%-60.2%), with a median OS of 26.0 months among all treated phase 2 patients (n = 55) and 38.9 months in patients with CR or CRi (n = 39).

Overall CR rate (CR + CRi), CR, and subsequent allogeneic stem cell transplant (alloSCT) rates remained unchanged since the prior data cutoff point at 71%, 56%, and 20%, respectively.

Median relapse-free survival (RFS) censored and not censored at subsequent alloSCT were 11.6 (2.7-20.5) and 11.7 (2.8-20.5) months, respectively.

For patients treated at the pivotal dose in both phase 1 and 2 (n = 78), the median follow-up at data cutoff was 41.6 months (range, 32.7-70.3). Median (95% CI) duration of response censored and not censored at subsequent alloSCT was 18.6 (9.6-24.1) and 20.0 (10.3-24.1) months, respectively.

Median RFS were both 11.7 (6.1-20.5) months.

At data cutoff, 36% of patients (28) were still alive with a median OS of 25.6 months (95% CI, 16.2-47.0) in all treated patients (n = 78).

The proportion of patients in both phases with grade 3 or higher adverse effects (AEs) was unchanged vs the prior cutoff. Additionally, there were no grade 5 AEs since the data cutoff.

Most patients in the analysis were heavily pretreated, with a median of 2 prior therapies, and 47% had received 3 or more prior therapies.

Reference

Kite’s Tecartus CAR T-cell therapy demonstrates overall survival benefit in three-year follow-up of pivotal ZUMA-3 trial in relapsed/refractory B-cell acute lymphoblastic leukemia. News release. Kite, a Gilead Company. February 9, 2023. Accessed February 9, 2023. bit.ly/3xc2CRk