Brexu-cel Clears CNS Disease in R/R B-Cell Acute Lymphoblastic Leukemia


Findings from a retrospective study demonstrate the feasibility of using brexucabtagene autoleucel to treat patients with relapsed/refractory B-cell acute lymphoblastic leukemia with central nervous system involvement.

“We did show the efficacy of brexu-cel in achieving CNS remission, and we confirmed the [agent’s] efficacy in achieving a systemic response," according to Ibrahim N. Muhsen, MD.

“We did show the efficacy of brexu-cel in achieving CNS remission, and we confirmed the [agent’s] efficacy in achieving a systemic response," according to Ibrahim N. Muhsen, MD.

Treatment with brexucabtagene autoleucel (brexu-cel; Tecartus) produced high rates of central nervous system (CNS) remission in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), according to findings from a retrospective study presented at the 2024 Tandem Meeting.1

Concerning systemic disease response, most patients had active disease (47.0%; n = 16/34) at the time of apheresis followed by complete responses (CRs) with minimal residual disease (MRD) positivity (29.4%; n = 10/34), CRs with MRD negativity (20.6%; n = 7/34), and 3.0% (n = 1) had a CR. At the time of the first disease assessment, a CR was reported in 85% (n = 29/34) of patients, which included a sustained CR and MRD negativity in 76.5% (n = 26/34). Additionally, a CR was highlighted in 81% (n = 13/16) of patients who had active disease.

At the time of apheresis, 50% (n = 17/34) of patients had CNS 2 disease–defined as having detectable blasts in cerebrospinal fluid (CSF) with fewer than 5 white blood cells per uL—and 50% (n = 17/34) had CNS 3 disease, which was defined as having detectable blasts and more than 5 white blood cells per uL. Of 9 evaluable patients who received bridging therapy, 8 had CNS 1 disease responses, which was defined as having no identifiable CNS disease. Five patients were treated with intrathecal chemotherapy plus systemic therapy. After bridging, 8 of 9 patients had a response.

Investigators reported that 88% (n = 22/25) of those with a CSF evaluation achieved a response, which included 12 patients with CNS 3 disease and 10 with CNS 2 disease who had no CNS involvement at the first disease reassessment. Of 10 patients who did not undergo bridging therapy, 9 achieved CNS clearance following CAR T-cell therapy.

Additional treatment following CAR T-cell therapy was reported in 26.5% (n = 9/34) of patients to prolong remission or prevent a relapse. Additionally, a relapse occurred in 38.2% (n = 13/34) of patients with a median time to relapse of 100 days (range, 6-263), and a relapse within the first 3 months occurred in 4 patients.

“Treating adult patients with CNS B-ALL with brexu-cel is feasible,” presenting author Ibrahim N. Muhsen, MD, a hematology and medical oncology fellow at Baylor College of Medicine, said. “We did show the efficacy of brexu-cel in achieving CNS remission, and we confirmed the [agent’s] efficacy in achieving a systemic response.”

Of note, Muhsen stated that although brexu-cel is the only CAR T-cell therapy currently approved by the FDA for patients with relapsed/refractory B-ALL based on data from the phase 2 ZUMA-3 trial (NCT02614066), the study only included 5 patients with CNS involvement and excluded those with symptomatic CNS disease or those with a high CSF white blood cell count.2 Consequently, safety and efficacy data of CAR T-cell therapy in CNS B-ALL disease appear to be limited.

Investigators collected data from the Real World Outcomes Collaborative for CAR T in ALL (ROCCO) consortium to assess outcomes in patients who received brexu-cel for relapsed/refractory B-ALL from October 2021 to October 2023. The data were collected from 226 patients who underwent apheresis to receive brexu-cel at 31 academic and community practices across the United States.

The study’s primary end points were safety and CNS responses. Investigators assessed immune effector cell-associate neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS) based on the American Society for Transplantation and Cellular Therapy (ASTCT) criteria.

Patients were classified as having CNS 1, which included those with no identifiable CNS disease; CNS 2; or CNS 3. Overall, 17 patients with CNS 2 disease and 17 with CNS 3 disease received treatment with brexu-cel and were included in the analysis.

The median age at the time of CAR T-cell therapy was 47 years (range, 24-76). Additionally, most patients were male (55.9%), had Philadelphia chromosome (Ph)–positive disease (41.2%; n = 14), CNS 1 disease at the time of diagnosis (73.5%; n = 25), and unknown extramedullary disease status (64.7%; n = 22). A systemic CR was highlighted in 53% (n = 18) of patients at the time of apheresis, including 7 who had MRD negativity; Muhsen stated that their disease was thus isolated to the CNS.

Patients received a median of 4 prior lines of therapy (range, 2-12), and most previously underwent allogeneic hematopoietic stem cell transplant (53.0%; n = 18). Additionally, 88% of patients (n = 30) received brexu-cel plus intrathecal chemotherapy.

Data highlighted receipt of bridging therapy among 67% of patients, with the most common types including systemic therapy only (48%), systemic treatment plus intrathecal chemotherapy (35%), and intrathecal chemotherapy alone (17%). Patients had a median time to infusion of 33 days (range, 5-194).

Any-grade CRS occurred in 73.5% (n = 25) of patients, including grade 3/4 events in 3% (n = 1). The median time to CRS onset was 5 days (range, 1-10), and events lasted for a median of 4 days (range, 1-10). Of note, 26.5% (n = 9) of patients did not have a CRS event.

Additionally, any-grade ICANS affected 76.6% (n = 23) of patients, which included grade 3/4 instances in 35.3% (n = 12). The median time to ICANS onset was 7 days (range, 3-15), and the median duration of this toxicity was 3 days (range, 1-30). Toxicity was generally managed with steroids (73.5%; n = 25) followed by tocilizumab (Actemra; 58.8%; n = 20) and anakinra (Kineret; 20.6%; n = 7).

Grade 3/4 CRS affected 3% (n = 1/34) of patients with CNS disease, 12% (n = 19/155) of patients without CNS disease whose data were included in the ROCCA consortium, and 24% (n = 13/55) of patients in the ZUMA-3 trial. Rates of grade 3/4 ICANS were 35.3% (n = 12/34), 30% (n = 47/155), and 24% (n = 13/55) in each respective group.


  1. 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
  2. FDA approves brexucabtagene autoleucel for relapsed or refractory B-cell precursor acute lymphoblastic leukemia. News release. October 1, 2021. Accessed February 22, 2024.
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