Real-World Data Shows Brexu-cel's Impact on Relapsed/Refractory B-Cell ALL

Microscopic image of red blood cells: © AkuAku - stock.adobe.com

Real-world data from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry showed the effectiveness of brexucabtagene autoleucel (Tecartus; brexu-cel) for the treatment of patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL).¹

In 2021, brexu-cel became the first CD19-directed chimeric antigen receptor (CAR) T-cell therapy to be approved by the FDA for adult patients with R/R B-cell ALL. Data from the phase 1/2 ZUMA-3 trial (NCT02614066) supported this regulatory decision and showed that treatment with brexu-cel achieved a high rate of complete remission (CR; 71%) or CR with incomplete hematologic recovery (CRi). A manageable safety profile was also observed among those included. Because of this, experts sought to evaluate the outcomes of brexu-cel in a broad, real-world patient population.

Ninety-one percent of patients in the real-world evaluation were deemed ineligible for the ZUMA-3 trial, most commonly due to low disease burden, with nearly 40% of patients having less than 5% bone marrow blasts, which was a minimum requirement for ZUMA-3. However the rates of CR without hematological recovery with brexu-cel in this population were consistent with those observed in the clinical trial population.

By day 100 postinfusion, the overall CR/CRi rate was 76% and 70% of patients were still in remission at 6 months after initial response (95% CI, 55%-80%). A total of 63% of patients who were not in response before lymphodepletion converted into a CR/CRi. Additionally, relapse-free survival at 6 months was 53% (95% CI, 42%-62%), and the overall survival rate at 6 months was 78% (95% CI, 69%-84%).

Despite the differences between the patient populations in the real-world and clinical settings, the efficacy of brexu-cel in this real-world analysis was consistent with what was observed in the clinical trial.

Evandro D. Bezerra, MD

In an interview with Targeted Oncology^TM, Evandro D. Bezerra, MD, the Ohio State Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute, discussed the real-world effectiveness of brexu-cel for relapsed/refractory B-cell ALL.

Targeted Oncology: Can you discuss brexu-cel and how it has been developed thus far?

Bezerra: Brexu-cel is a CD19 CAR T-cell therapy for patients with relapsed/refractory B-cell ALL and also other B-cell malignancies. [These] data show the real-world outcomes of brexu-cel since it was approved as a standard –of care for this patient population. [These data] show that the brexu-cel is highly effective in the real-world setting, consistent with the data from the ZUMA-3 clinical trial, despite the significant difference between the patient populations in the ZUMA-3 clinical trial and the real-world population.

Can you provide some background on ZUMA-3?

The ZUMA-3 clinical trial was the pivotal trial that led to the approval of brexu-cel for relapsed/refractory B-cell ALL. [In] that trial, patients with relapsed/refractory B-cell ALL received brexu-cel, and they had high efficacy, with CR rates of 71%, and patients that responded had a median overall survival of 47 months.

How does the real-world population compare with the clinical trial population?

A very interesting finding of our research was that 91% of the patients would not be or would potentially be ineligible to submit to clinical trials, showing a difference of the patient population of treating the trial in the real-world patient population. One of the most common reasons was a low disease burden, and around 40% of our patients had less than 5% bone marrow blasts. That was the minimum requirements in the clinical trial. And despite this difference, the real-world setting showed that patients who had brexu-cel were highly effective.

Were there any specific subgroups of patients who responded well or poorly to brexu-cel?

Another interesting finding of our data is that is the subgroup analysis that we performed by looking at patients that were in [complete response] or not, had [minimal residual disease (MRD)] or not, had prior blinatumomab [Blincyto] or not, had the extramedullary disease or not, had a prior transplant or not, did not see a significant difference in the effective outcomes, like [complete response rate], relapse-free survival, [and] overall survival.

How do the rates of cytokine release syndrome (CRS) and other adverse events compare with what was seen in ZUMA-3?

They are consistent. We saw an 80% rate of CRS, 9% of CRS that was grade 3 or higher, 47% rates of [immune effector cell-associated neurotoxicity syndrome (ICANS)], and 23% of rates of grade 3 or higher ICANS. This is similar to the scene in the ZUMA-3 clinical trial, showing that brexu-cel has a safety profile consistent to that seen in the ZUMA-3 clinical trial and is manageable in the real-world setting.

For a community oncologist, what would you say are the key takeaways from this research?

One of the main takeaways is that in the ZUMA clinical trial, patients had a minimal requirement of 5% blasts in the bone marrow to be eligible for the treatment. In the real-world setting, a lot of these patients are receiving brexu-cel with less than 5% bone marrow blasts. Despite this, brexu-cel still remains effective. Even the patients that are responding to salvage therapy or bridging therapy, they still respond to brexu-cel, and the patients should be considered to receive brexu-cel, despite having lower disease [burden].

REFERENCE:

Bezerra E, Itani T, Wudhikarn K, et al. Real-world outcomes of brexucabtagene autoleucel (brexu-cel) for relapsed or refractory (R/R) adult B-cell acute lymphoblastic leukemia (B-cell ALL): evidence from the CIBMTR registry. Blood. 2023;142(suppl 1):1029. doi:10.1182/blood-2023-174543