How Do Young Adults Receiving CAR T-Cell Therapy for R/R B-ALL Fare in the Real World?

Treatment options for relapsed/refractory B-cell acute lymphoblastic leukemia have evolved over the last few years with the emergence of multiple chimeric antigen receptor (CAR) T-cell therapies. Previously, patients received chemotherapy or other salvage therapy prior to a hematopoietic cell transplantation (HCT). Now there’s a big question as to what impact CAR T-cell therapy has on patients’ overall trajectory and how various CAR T-cell products differ.

Cleveland Clinic Cancer Institute recently participated in a multicenter retrospective study analyzing these questions. Published in Blood Advances, the study found complete response rates were comparable between the two CD19-directed CAR T-cell products FDA approved for young adults with relapsed/refractory (R/R) B-ALL: Tisagenlecleucel (tisa-cel) and brexucabtagene autoleucel (brexu-cel).

A higher percentage of patients receiving the CAR T-cell product brexu-cel experienced adverse events such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) compared to those receiving tisa-cel.

Background

For B-ALL patients, hematologists usually recommend CAR T-cell therapy as a bridge to transplant or when patients aren’t a transplant candidate. However, there has been no published data specifically about the outcomes of young adults with B-ALL receiving this treatment.

This is a concerning knowledge gap, since clinicians are seeing higher rates of B-ALL in adolescents and young adults. This population has experienced inferior outcomes as a result of many factors, such as lower tolerance for intensive chemotherapy and early treatment discontinuation. Young adults also tend to have higher risk genetic factors, such as Ph-like B-ALL, including alterations such as BCR:ABL1 fusion and KMT2A-rearranged B-ALL.

Additionally, clinicians are looking to better understand the mechanisms of action of each CAR T-cell product. Tisa-cel includes a 41BB costimulatory domain, which was shown to stimulate longer CAR T-cell persistence in preclinical studies. Brexu-cel uses a CD28 costimulatory domain.

Some studies have shown improved outcomes for CAR T-cell therapy followed by consolidated HCT, yet determining which patients will benefit from this course remains problematic. “Since the positive outcomes of the ELIANA trial with pediatric patients, including young adults, there’s been a whole debate about whether we still need to transplant those patients,” says Cleveland Clinic Cancer Institute Hematologist/Oncologist Anjali Advani, MD, who is a co-author of the study.

“In thinking about the young adult population specifically, we wanted to understand if they still needed transplant and also how the two CAR T-cell products are different in terms of efficacy for this population. Since the co-stimulatory domain is different between the two products, there’s been some question about CAR T-cell persistence and its role in outcomes.”

Study design

In this latest study, researchers analyzed retrospective data from the Pediatric Real-World CAR T Consortium and the Real-World Outcomes of CAR T in Adult ALL (ROCCA) databases. These included patients ages 18-26 years old treated at 40 different sites across the U.S.

Data for 374 patients was included, with the primary outcomes of 12-month overall survival, relapse-free survival and duration of remission. Secondary outcomes included toxicity and overall response rates.

Study outcomes

Complete response rates were similar between the two products (80% in patients receiving brexu-cel and 88% in patients receiving tisa-cel). The majority of patients (86% of tisa-cell patients and 70% of brexu-cel patients) had undetectable minimal residual disease). A 12-month follow-up found relapse-free survival rates of 46% for brexu-cel patients and 36% for tisa-cel patients. After CAR T-cell therapy, 11 patients proceeded with a HCT (seven patients in the brexu-cel cohort and four in the tisa-cel cohort.)

“I would have thought that patients who received tisa-cell would have much better outcomes due to the costimulatory domain but that wasn’t the case,” notes Dr. Advani. “This could have been due to any number of factors, however, such as the fact that patients were heavily pretreated. We may see differences in efficacy emerge as we continue follow-up over time.”

In terms of side effects, patients receiving brexu-cel were more apt to experience cytokine release syndrome (CRS), with 85% patients in this cohort having CRS to some degree, compared to 56% of patients in the tisa-cell cohort. In terms of ICANS, 40% of patients receiving brexu-cell experienced any grade ICANS, compared to 18% in the tisa-cell group.

The median survival was 23.5 months in the tisa-cel cohort and was not reached in the brexu-cel cohort. Eighteen patients (15% on the brexu-cel cohort and 30% in the tisa-cel cohort) passed away as a result of relapsed disease, infection or acute respiratory distress syndrome.

Researchers also studied factors that impacted overall survival and relapse-free survival. Lower disease burden at infusion seemed to be a factor but did not achieve statistical significance.

Dr. Advani was quick to point out several caveats about the study findings. First, the numbers are still smaller than the researchers would like. “It would be great to see a larger cohort comparison,” she says. “This was not a head-to-head comparison.”

The study was also notable for having a sizeable percentage of Hispanic patients (37%), which may have skewed the data to some degree since more Hispanic patients have Ph-like B-ALL, which has a higher risk biology.

What’s next

A third CD19-directed CAR T-cell therapy called obecabtagene autoleucel (obe-cel) was FDA approved in November 2025 to treat R/R B-ALL. “The ROCCA Consortium is planning to study this product, and as time goes on we’ll likely have a cohort of young adult population receiving this therapy,” says Dr. Advani. “The initial trial for this therapy found patients experiencing less CRS with obe-cell so it will be interesting to see studies of real-world data.”

The study authors also noted that further research is needed to help understand and address barriers to receiving this emerging therapy, which is primarily available at tertiary cancer care centers.