Brexu-cel Achieves Strong CNS and Systemic Responses in Adult B-ALL Patients

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Brexucabtagene autoleucel (brexu-cel; Tecartus) demonstrated notable efficacy through the achievement of high rates of central nervous system (CNS) remission among patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), according to data collected from the Real World Outcomes Collaborative for chimeric antigen receptor (CAR) T in ALL (ROCCO) consortium.¹

Data were collected from 226 patients who underwent apheresis to receive brexu-cel at 31 academic and community practices across the US. Primary end points of the study included safety and CNS responses. Additionally, immune effector cell-associate neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS) were evaluated based on the American Society for Transplantation and Cellular Therapy criteria.

At apheresis, 47.0% (n = 16) of patients had active disease, 29.4% (n = 10) achieved complete responses (CRs) with minimal residual disease (MRD) positivity, 20.6% (n = 7) had CRs with MRD negativity. At the first disease assessment, 85% (n = 29/34) of patients had a CR, with 76.5% (n = 26/34) showing sustained CR and MRD negativity. Among those with active disease at apheresis, 81% (n = 13/16) attained CR by the first disease assessment.

Looking at CNS responses, 88% (n = 22/25) of patients with cerebrospinal fluid (CSF) evaluation achieved a response. CNS 2 disease (blasts in CSF with <5 WBC/μL) and CNS 3 disease (blasts with >5 WBC/μL) were evenly distributed among the patients. Bridging therapy led to CNS 1 disease responses (no detectable CNS disease) in 8 of 9 evaluable patients, with intrathecal chemotherapy combined with systemic therapy in 5 cases. Following CAR T-cell therapy, 9 of 10 patients who did not receive bridging therapy achieved CNS clearance.

CRS was observed in 73.5% (n = 25) of patients, with grade 3/4 CRS occurring in only 3% (n = 1). The median onset of CRS was 5 days, lasting for a median of 4 days. Notably, 26.5% (n = 9) of patients did not experience CRS. ICANS occurred in 76.6% (n = 23) of patients, with 35.3% (n = 12) experiencing grade 3/4 ICANS. The median time to ICANS onset was 7 days, and the median duration was 3 days.

In an interview with Targeted Oncology^TM, Ibrahim N. Muhsen, MD, a hematology and medical oncology fellow at Baylor College of Medicine, evaluated the efficacy of brexu-cel in achieving both CNS and systemic responses in adult patients with CNS involvement in relapsed/refractory B-ALL.

Targeted Oncology: What was the rationale or the inspiration for this research?

Muhsen: Patients with relapsed/refractory ALL who have CNS involvement have very limited efficacious therapies. This includes the newer targeted therapies, which have very limited evidence of CNS activity.

When it comes to CAR T cells, we have few studies, mainly retrospective and post hoc analyses of prospective data, that show some activity in the CNS, particularly for [tisagenlecleucel (Kymriah)]. In 2021, brexu-cel was approved for adult patients with ALL. However, so far, we have no evidence that brexu-cel will have activity in patients with CNS ALL. So, this is a retrospective study of the efficacy and safety of brexu-cel in patients with CNS ALL in the relapsed/refractory setting.

What were the goals of this study?

[We wanted] to look into the safety and efficacy of brexu-cel in adult patients who have CNS involvement at the relapse of ALL. We utilized the real-world outcomes of adult patients with ALL consortium data, which is a consortium that includes 31 different institutions, both academic and community institutions. The consortium has data on more than 200 patients [with ALL] that were treated with brexu-cel. Out of these patients, we found 34 patients who had CNS ALL at relapse and received CAR T-cell therapy for that.

Can you discuss the findings from this study?

When it comes to the safety of brexu-cel, [for] our patient population that has a very low rate of high-grade CRS, we actually had only 1 patient that had grade 3 to 4 CRS. On the other hand, when it comes to ICANS, we had a higher number of patients who had grade 3 to 4 ICANS of 35%. However, when we compared the numbers to the number of patients who develop the grade 3 to 4 ICANS in the ROCCA consortium database without CNS involvement, the numbers were similar.

Additionally, when it comes to the efficacy of the CAR T cells, we did see that our patients had a very high CNS response rate. We had 22 patients who showed response out of 25 who were evaluated, which is almost more than 85% of patients who achieved CNS1 status or no CNS disease after the CAR T-cell therapy. Our findings are very encouraging for the use of CAR T-cell therapy in patients who have CNS B-ALL. However, more studies are needed to confirm these results.

What are the key takeaways for a community oncologist as a result of this study?

Our findings are encouraging for the use of CAR T-cell therapy in patients who have CNS ALL. However, more studies are needed to confirm these results.

REFERENCE:

Muhsen IN, Roloff G, Kopmar NE, et al. Assessment of central nervous system responses in adults with relapsed/refractory B-cell acute lymphoblastic leukemia receiving brexucabtagene autoleucel as an FDA-approved standard of care. Transplantation and Cellular Therapy. 2024;30(2):S7-S8. doi:10.1016/j.jtct.2023.12.028