CAR T-Cell Therapy Outcomes Likely Not Influenced by Race/Ethnicity, Obesity

Researchers studied data from 5 phase 1 studies that took place between 2012 and 2021, comprising 139 infusions among patients with B-cell acute lymphoblastic leukemia who received chimeric antigen receptor (CAR) T-cell treatment.

Chimeric antigen receptor (CAR) T-cell therapy may provide clinical benefit across a range of patients with hematologic malignancies and historically inferior outcomes following traditional cancer treatments like chemotherapy, according to an analysis that showed outcomes of the treatment approach were not affected by race, ethnicity, or obesity.

Findings published recently in Blood Advances.

However, the analysis indicated that Hispanic patients were at a higher risk of cytokine release syndrome (CRS), the most common toxicity associated with CAR T cells. Based on their findings, the researchers of the study cited a need for improved access to CAR T-cell therapy among underrepresented populations and an improved understanding of varying toxicity among these groups.

The group noted that to date, it’s been difficult to answer if CAR T-cell therapy can benefit racial/ethnic monitories and patients with obesity, largely because these groups lack representation in clinical trials. For example, the first 2 randomized trials of CAR T-cell therapy in the United States had cohorts that included less than 10% of Hispanics or Blacks.

“Given the tremendous potential of CAR T-cell therapy to overcome chemotherapy-resistant and refractory disease, understanding whether its benefits extend equally to racial and ethnic minorities and patients with obesity is of critical importance to assessing the generalizability of existing outcome data for this novel cancer treatment modality and potentially improving outcomes for the highest-risk populations,” explained the researchers.

In the current analysis, the researchers studied data from 5 phase 1 studies that took place between 2012 and 2021, comprising 139 infusions among patients with B-cell acute lymphoblastic leukemia (B-ALL).

Among the patients, 28.8% were Hispanic. Compared with non-Hispanic White patients, Hispanic patients were significantly more likely to experience CRS (odds ratio [OR], 4.5; P = .001) and had a 3-fold increased risk of experiencing grade ≥ 3 CRS (OR, 4.0; 95% CI, 1.23-8.54; P = .001).

“Importantly, other factors not evaluated in this study, such as lymphodepletion regimens and CAR manufacturing nuances, have also been implicated with CRS severity, and therefore additional work is required to elucidate whether these factors might impact the toxicity disparities we found,” described the researchers. “Notably, extremes of BMI [body mass index] have been associated with greater toxicity with conventional leukemia therapy, and although our study failed to show an association between BMI and CRS severity in general, we did find Hispanic patients who were overweight or obese were at the highest risk for severe CRS in our cohort.”

Meanwhile, the researchers found that efficacy was similar between different groups. Complete response rates, achieved in 67.6% of patients, were comparable between Hispanic and non-Hispanic White patients (OR, 0.67; 95% CI, 0.30-1.50; P = .33), other non-Hispanic and non-Hispanic White patients (OR, 0.81; 95% CI, 0.29-2.25; P = .67), and between patients who were overweight/obese and those who were not (OR, 0.74; 95% CI, 0.34-1.60; P = .44. Close to a third (29.5%) of patients were considered overweight or obese. Similar findings were observed for overall survival rates.

The 5 trials in the analysis also included 24 patients with multiple myeloma and 23 patients with non-Hodgkin lymphoma; both cohorts showed patterns similar to those seen among the patients with B-ALL.

The researchers noted that due to limited representation of Black and African American patients in the studies, they were unable to do inferential statistical comparisons for these patients.

Reference

Faruqi AJ, Ligon JA, Borgman PG, et al. The impact of race, ethnicity, and obesity on CAR T-cell therapy outcomes. Blood Adv. Published online August 8. doi:10.1182/bloodadvances.2022007676