Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed CAR T-cell therapy approved for adults with relapsed or refractory B-ALL. It redirects a patient’s T cells to target CD19-positive B cells, offering a potentially curative option. Following its approval based on high CR/CRi rates in the Phase II ZUMA-3 trial, updated 5-year data from Phase I/II cohorts were presented at EHA 2025 to assess long-term efficacy and safety.

As of July 23, 2024, the median follow-up duration for adult patients (≥18 years; N=78) in Phases 1 and 2 was 65.7 months. Median overall survival (OS) remained consistent with the 4-year analysis at 25.6 months, and the 5-year OS rate was 40%. Patients who achieved a complete response (CR) or complete response with incomplete hematologic recovery (CRi) per central review (n=57) had a median OS of 60.4 months, while those with a CR (n=47) had not yet reached median OS.

Among patients aged ≥26 years (n=63), the median follow-up was 65.6 months with a stable median OS of 26.0 months since the previous analysis and a 5-year OS rate of 42%.

The 5-year OS rates varied based on prior treatments:

• With vs. without prior blinatumomab: 25% vs. 54%

• With vs. without prior inotuzumab: 21% vs. 45% 

• With vs. without previous alloSCT: 36% vs. 42% 

Among patients who responded to treatment (per investigator review, n=58), those who underwent subsequent allogeneic stem cell transplant (n=14) had a median OS of 50.2 months, while those who did not receive a transplant (n=44) had a median OS of 60.4 months. Their 5-year OS rates were 42% and 52%, respectively.

Since the 4-year analysis, one new adverse event (cervical cancer) and one death (due to pulmonary failure) were reported in the same patient; both events were deemed unrelated to brexucabtagene autoleucel (brexu-cel). Importantly, no secondary T-cell malignancies were observed in the ZUMA-3 trial.

At the time of data cutoff, 44 out of 78 patients (56%) had died, 20 (26%) were still alive, and 14 (18%) were either lost to follow-up or had withdrawn consent. The estimated 60-month cumulative incidence of death was 34% from disease progression and 26% from non-disease-related causes.

KOL insights

“While a significant number of Acute Lymphoblastic Leukemia patients experience relapse, the demand for effective treatments in this population remains unmet. However, there has been rapid progress in the development of newer therapies.” – Expert Opinion

“In pediatric acute lymphoblastic leukemia, modern risk-directed treatments have achieved 5-year overall survival rates surpassing 90%. Efforts now concentrate on enhancing outcomes and reducing intensive therapy-related toxicity through expanded utilization of immunotherapy, identification of targetable genetic anomalies, and refinement of risk assessment accuracy.”– Expert Opinion

Conclusion

The ALL treatment landscape is advancing rapidly, shifting from traditional chemotherapy to targeted immunotherapies and cell-based approaches. One of the most significant advancements in leukemia treatment has been the introduction of CAR-T cell therapy. This approach has shown great promise for patients with relapsed leukemia who have exhausted other treatment options. CAR-T cell therapy involves modifying T cells by inserting an antibody that enables them to recognize and destroy leukemic blasts. It appears to be more powerful than blinatumomab. Research is ongoing to explore new applications of CAR-T cells, and currently, two different CAR-T cell therapies are available.

CAR-T therapies like TECARTUS and KYMRIAH offer deep remissions in R/R cases. Usage of KYMRIAH and stem cell transplantation will mainly be reserved for third line and above patients. CAR-T cell therapies as a class are expected to take around 60% share by 2030 in the third line and above setting. Around 5 CAR-T cell therapies are expected to enter the market by 2030 set to impact the market of current approved drugs.