Peak CAR T-Cell Expansion Linked to Improved Outcomes in B-ALL Patients Receiving Brexu-Cel
Key Insights
Peak CAR T-cell expansion of 15 cells/μL or greater following brexucabtagene autoleucel treatment was associated with reduced relapse risk in B-cell acute lymphoblastic leukemia (search) patients with low disease burden.
Real-world data from 52 patients showed 12-month overall survival and relapse-free survival rates of 89% and 66%, respectively, with only 2 relapses among patients achieving high CAR T-cell expansion.
The study demonstrates that brexu-cel (search) maintains efficacy even in patients with CNS involvement, with comparable toxicity profiles between CNS-positive and CNS-negative cohorts.
New real-world evidence suggests that peak CAR T-cell expansion serves as a critical biomarker for predicting treatment outcomes in patients with B-cell acute lymphoblastic leukemia (search) (B-ALL (search)) receiving brexucabtagene autoleucel (brexu-cel (search); Tecartus). Data presented at the 2025 SOHO Annual Meeting revealed that patients achieving peak CAR T-cell expansion of 15 cells/μL or greater experienced significantly lower relapse rates compared to those with lower expansion levels.
Expansion Threshold Predicts Clinical Outcomes
In a retrospective analysis of 52 adult patients with low tumor burden treated at The University of Texas MD Anderson Cancer Center, researchers established a critical threshold for peak CAR T-cell expansion at 15 cells/μL. At a median follow-up of 16.1 months, patients in the overall cohort achieved 12-month overall survival (OS) and relapse-free survival (RFS) rates of 89% and 66%, respectively.
The study revealed striking differences in outcomes based on expansion levels. Among patients achieving peak CAR T-cell expansion of 15 cells/μL or greater (n = 25), only 2 relapses were reported. The 12-month RFS rates were 81% versus 71% in NGS MRD-negative patients with peak CAR T-cell expansion of 15 cells/μL or greater versus less than 15 cells/μL, respectively.
"It is clear that the patients who underwent CAR T-cell infusion while MRD positive had rapid relapse events if they did not have any peak CAR T-cell expression greater than 15 [cells/μL]," stated Niranjan Khaire, MBBS, MD, DM, a first-year fellow in the Leukemia Clinical Fellowship Program at MD Anderson. "This is a very high-risk cohort for which some additional therapy is warranted once we see that there is not adequate CAR T-cell expansion."
Disease Burden Influences Expansion Patterns
The analysis revealed distinct patterns of CAR T-cell expansion based on pre-treatment minimal residual disease (MRD) status. Among 38 patients who were NGS MRD-negative at the time of CAR T infusion, 44% exhibited peak CAR T-cell expansion of 15 cells/μL or greater, with a median peak expansion of 11 cells/μL. In contrast, among 14 NGS MRD-positive patients, 57% achieved high expansion levels, with a significantly higher median peak expansion of 36.5 cells/μL.
Patient characteristics also influenced expansion patterns. Philadelphia chromosome (Ph)-positive disease (P = .019) and absence of prior inotuzumab exposure (P = .008) were significantly associated with higher CAR T-cell expansion. Among patients with Ph-positive ALL, 72% demonstrated peak CAR T-cell expansion of 15 cells/μL or greater, while only 38% of patients who received prior inotuzumab achieved high expansion levels.
CNS Involvement Does Not Compromise Efficacy
Complementary data from the Real-World Outcomes Collaborative for CAR T in ALL (search) (ROCCA) consortium demonstrated that brexu-cel (search) maintains efficacy even in patients with central nervous system (CNS) involvement, a population historically excluded from clinical trials. The multi-institutional study analyzed 189 patients, including 31 with CNS involvement.
Toxicity profiles were comparable between patients with and without CNS involvement. In the CNS group, 74.2% developed cytokine release syndrome (search) (CRS), with only one case of grade 3/4 severity, while 64.5% experienced immune effector cell-associated neurotoxicity syndrome (search) (ICANS), including 11 patients with grade 3/4. These rates mirrored the non-CNS cohort, in which 84.8% had CRS (12.0% were grade 3/4) and 54.4% had ICANS (30% were grade 3/4).
The cumulative incidence of relapse at 1 year was 39% in the CNS group compared with 35% in patients without CNS disease (P = .54). The 6- and 12-month progression-free survival in the CNS group were 57% and 47%, respectively, with a median PFS of 263 days. No statistically significant differences in PFS or OS were observed between CNS and non-CNS groups.
Safety Profile Remains Manageable
In the low tumor burden cohort, brexu-cel (search) demonstrated a manageable safety profile. Any-grade CRS was observed in 54% of patients, with only 2% experiencing grade 3 events and no grade 4 CRS reported. ICANS events occurred in 21% of patients, with 6% grade 3 and 4% grade 4. Notably, patients with grade 2-4 CRS or ICANS had high CAR T expansion levels (102-2222 cells/μL).
Post-treatment hematologic toxicities included grade 3/4 neutropenia in 10% of patients at day 28 and grade 3/4 thrombocytopenia in 33% at day 28. CRS/ICANS events were managed with tocilizumab in 42% of patients, dexamethasone in 25%, and intensive care support in 13%.
Clinical Implications for Monitoring
The findings suggest that CAR T-cell expansion monitoring could guide post-treatment decisions in clinical practice. Khaire emphasized that "even in the clinical settings, CAR T-cell expansion should be monitored to help guide post-CAR T-cell treatment decisions," particularly for high-risk patients who fail to achieve adequate expansion.
The research builds on the FDA approval of brexu-cel (search) in October 2021 for adult patients with relapsed or refractory B-cell precursor ALL, based on the registrational ZUMA-3 trial showing a 52% complete response rate. These real-world studies extend the evidence base to include patients with low disease burden and CNS involvement, populations not extensively studied in the original registration trial.