Treatment with brexucabtagene autoleucel (brexu-cel; Tecartus) demonstrates comparable efficacy in patients aged 60 to 69 with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) compared to those under 60, according to a real-world study presented at the 2024 ASH Annual Meeting. The study, which analyzed data from 318 patients across 40 US-based institutions, suggests that brexu-cel is a feasible treatment option for older adults with B-ALL, despite limited data on this population.
Comparable Remission Rates Across Age Groups
The study found that patients under 60 (n = 220) achieved a complete remission (CR)/CR with incomplete count recovery (CRi) rate of 89%, with a minimal residual disease (MRD)-negativity rate of 74%. Patients aged 60 to 69 (n = 57) also experienced a CR/CRi rate of 89%, with an MRD-negativity rate of 59%. In patients 70 years or older (n = 19), the CR/CRi rate was 94% with an MRD-negativity rate of 67%.
"The rates of CR were similar across the groups at approximately 90%, and no statistically significant difference was detected between the groups," said Dr. Ibrahim Muhsen of Baylor College of Medicine in Houston, Texas, during the presentation. He noted that MRD-negativity rates were numerically lower among patients aged 60 to 69 compared with other groups.
Survival Outcomes
Overall survival (OS) showed no significant differences between the age groups. The median OS values were 695 days for those under 60, not yet reached for the 60-69 group, and 673 days for those 70 and older (log-rank P = .8). The 6-month OS rates were 81%, 81%, and 73%, respectively, and the 12-month OS rates were 68%, 63%, and 61%, respectively.
Progression-free survival (PFS) also showed no significant difference by age. The median PFS values were 397 days, 393 days, and 259 days for the under 60, 60-69, and 70-plus age groups, respectively (log-rank P = .8). The 6-month PFS rates were 64%, 58%, and 56%, respectively, and the 12-month PFS rates were 51%, 52%, and 38%.
Dr. Muhsen cautioned that the 12-month PFS rate and median PFS were lower in patients aged 70 and above, but the small sample size in that group makes it difficult to draw definitive conclusions. He added that longer follow-up is needed to better estimate the potential for cure with this approach.
Safety Profile
The safety findings were largely consistent across age groups. Any-grade cytokine release syndrome (CRS) occurred in 84%, 86%, and 89% of patients in the under 60, 60-69, and 70-plus age groups, respectively (P = .8). Grade 3 to 4 CRS occurred at rates of 11%, 4%, and 11%, respectively (P = .2). Any-grade immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 48%, 56%, and 79% of patients, respectively (P = .03), with grade 3 to 4 ICANS occurring in 29%, 30%, and 32% of patients, respectively (P = .9).
Hematotoxicity, as measured by median time to absolute neutrophil count recovery, was similar across groups: 16 days (IQR, 12-34), 15 days (IQR, 12-22), and 15 days (IQR, 11-19) in the under 60, 60-69, and 70-plus years old groups, respectively. Median times to platelet recovery were 27 days (IQR, 9-42), 31 days (IQR, 10-58), and 51 days (IQR, 27-63), respectively.
Rates of growth factor transfusion support and infections were not higher in older patients. Patients in all three arms required intravenous immunoglobulin infusion within 90 days (28% vs 18% vs 17%), granulocyte colony-stimulating factor (GCSF) use within 30 days (43% vs 33% vs 33%), GCSF use within 30 to 90 days (37% vs 30% vs 33%), thrombopoietin mimetics use on days 30 to 90 (6% vs 6% vs 6%), and red blood cell transfusion from days 30 to 90 (14% vs 22% vs 6%).
Context and Implications
Brexu-cel was the first CAR T-cell therapy approved by the FDA for adult patients with relapsed or refractory B-cell precursor ALL in October 2021, based on the ZUMA-3 trial. However, that trial included only a small number of older patients. This real-world study provides valuable data on the use of brexu-cel in a larger cohort of older patients, confirming its feasibility and efficacy in this population.
"Our data support and confirm that treating patients with B-ALL age 60 and older with brexu-cel is feasible," Dr. Muhsen concluded. "Longer follow-up and a larger sample size, particularly in the 70-plus age group, are needed."
