Tecartus CAR-T shows long-term durability among adults with advanced B-cell ALL
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Brexucabtagene autoleucel continued to confer a greater than 70% complete remission rate among adults with relapsed or refractory B-cell acute lymphoblastic leukemia, results from the latest analysis of a pivotal phase 2 study showed.
Three-year follow-up data from the ZUMA-3 trial presented at European Society for Blood and Marrow Transplantation-European Hematology Association (EHA) 5th European CAR T-cell Meeting revealed median OS of 26 months among those who received brexucabtagene autoleucel (Tecartus, Kite Pharma/Gilead Sciences). Median OS increased to 38.9 months among patients who had complete remission or complete remission with incomplete hematologic recovery after a single infusion of the CD19-directed chimeric antigen receptor T-cell therapy .
“For adult patients living with ALL, there is a need for therapeutic options that provide long-term responses,” Bijal D. Shah, MD, ZUMA-3 investigator and medical oncologist at Moffitt Cancer Center said in a Kite-issued press release. “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.”
Background
According to the ZUMA-3 investigators, the typical prognosis is poor for adults with relapsed or refractory B-cell precursor ALL, with an approximate median OS of less than 8 months despite the development of newer therapies, such as blinatumomab (Blincyto, Amgen) and inotuzumab ozogamicin (Besponsa, Pfizer).
Positive results from the ZUMA-3 trial led to FDA approval of the therapy in October 2021 for adults with relapsed or refractory B-cell ALL.
To assess the treatment’s durability, the ZUMA-3 investigators conducted a 3-year follow-up analysis of patients treated in the phase 2 portion (n = 55) and a pooled analysis of phase 1 and phase 2 patients who received the pivotal recommended phase 2 dose of brexucabtagene autoleucel (n = 78).
Methodology
Patients underwent lymphodepleting chemotherapy and then received a single infusion of brexucabtagene autoleucel at a recommended phase 2 dose of 1 × 106 CAR T cells/kg.
Complete remission (CR) rate — defined as those with CR plus complete remission with incomplete hematologic recovery (CRi) — served as the study’s primary endpoint. Secondary endpoints included duration of response, RFS, OS and safety.
Median follow-up was 38.8 months (range, 32.7-44.6) for those treated during the phase 2 portion of the study. Median follow-up was 41.6 months (range, 32.7-70.3) for patients treated at the pivotal recommended phase 2 dose in the pooled analysis.
July 23, 2022, served as the data cutoff point.
Key findings
Investigators reported unchanged overall CR/CRi (71%) and CR (56%) rates among phase 2 participants since the previous 2-year follow-up evaluation.
Further evaluation showed median OS of 38.9 months (95% CI, 21.9-not estimable) among phase 2 participants who had CR/CRi compared with 47 months (95% CI, 23.2-NE) for the phase 1/phase 2 pooled analysis.
Researchers noted median OS of 26 months (95% CI, 16.2-not estimable) for all patients during the phase 2 portion of the study, compared with 25.6 months (95% CI, 16.2-47.0) for the phase 1/phase 2 pooled analysis.
Patients with CR to therapy during the phase 2 portion of the study had a median duration of response of 20 months (95% CI, 9.6-24.1) compared with 17.6 months for the pooled phase 1/phase 2 analysis (95% CI, 9.6-23.6).
No grade 5 treatment-related adverse events occurred since the previous 2-year follow-up analysis. Likewise, no new-onset cases of cytokine release syndrome, neurotoxicity or hypogammaglobinemia occurred during the additional follow-up period.
Clinical implications
The longer follow-up and expanded data set showed that a single infusion of brexucabtagene autoleucel had a median OS of almost 4 years among patients who had a complete response to therapy in the pooled analysis.
“We are encouraged by the sustained benefit that a single one-time treatment of Tecartus continues to provide for patients living with this difficult-to-treat blood cancer,” Frank Neumann, MD, PhD, senior vice president and global head of clinical development at Kite said in the release. “Our hope is that these results, along with our commitment to long-term research of Tecartus, will continue to provide clarity to physicians on optimal treatment methods for these patients living with this rare disease who have suffered historically poor outcomes.”
References:
- Gilead Sciences. 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 (press release). Available at: https://www.gilead.com/news-and-press/press-room/press-releases/2023/2/kites-tecartus-car-t-cell-therapy-demonstrates-overall-survival-benefit-in-three-year-follow-up-of-pivotal-zuma-3-trial-in-relapsedrefractory-b-cel. Published Feb. 9, 2023.
- Hadjivassileva T, et al. Poster 34. Presented at: European Society for Blood and Marrow Transplantation-European Hematology Association 5th European CAR T-cell Meeting; Feb. 9-11, 2023; Rotterdam, Netherlands.
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Hadjivassileva T, et al. Poster 34. Presented at: European Society for Blood and Marrow Transplantation-European Hematology Association 5th European CAR T-cell Meeting; Feb. 9-11, 2023; Rotterdam, Netherlands.
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