The impact of race, ethnicity, and obesity on CAR T-cell therapy outcomes

Abstract

Cancer outcomes with chemotherapy are inferior in patients of minority racial/ethnic groups and those with obesity. Chimeric antigen receptor (CAR) T-cell therapy has transformed outcomes for relapsed/refractory hematologic malignancies, but whether its benefits extend commensurately to racial/ethnic minorities and patients with obesity is poorly understood. With a primary focus on patients with B-cell acute lymphoblastic leukemia (B-ALL), we retrospectively evaluated the impact of demographics and obesity on CAR T-cell therapy outcomes in adult and pediatric patients with hematologic malignancies treated with CAR T-cell therapy across five phase I clinical trials at the National Cancer Institute (NCI) from 2012 to 2021. Among 139 B-ALL CAR T-cell infusions, 28.8% of patients were Hispanic, 3.6% were Black, and 29.5% were overweight/obese. No significant associations were found between race, ethnicity, or body-mass index (BMI) and complete remission rates, neurotoxicity, or overall survival. Hispanic patients were more likely to experience severe cytokine release syndrome compared to white non-Hispanic patients even after adjusting for leukemia disease burden and age (odds ratio 4.5, p = 0.001). A descriptive analysis of patients with multiple myeloma (n=24) and NHL (n=23) displayed a similar pattern to the B-ALL cohort. Our findings suggest CAR T-cell therapy may provide substantial benefit across a range of demographics characteristics, including for those populations who are at higher risk for chemotherapy resistance and relapse. However, toxicity profiles may vary. Therefore, efforts to improve access to CAR therapy for underrepresented populations and elucidate mechanisms of differential toxicity among demographic groups should be prioritized.

A noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children

“…Further research is warranted to fully understand the contribution of genetic variation to this disparity in ALL incidence and how this can impact other clinical endpoints beyond the risk of developing ALL that demonstrate racial/ethnic disparities, such as overall survival, risk of relapse, and cytokine release syndrome with chimeric antigen receptor T cell therapy. 4 , 51 , 52 …”

Impact of race/ethnicity and language preferences on pediatric ALL survival outcomes

“…Thus, Spanish‐speaking patients may have been excluded from studies evaluating these regimens, even though census data reports that Hispanics make up the second largest ethnic group after Non‐Hispanic Whites 25,26 . In some pediatric leukemia clinical trials, disparities have been demonstrated in degrees of enrollment as well, with Hispanic and Non‐Hispanic Black patients enrolled to a lesser degree than Non‐Hispanic White patients 25,27 . Winestone et al demonstrated that early mortality was actually decreased among patients enrolled on a clinical trial, compared with those unenrolled 27 .…”

“…Hispanics are underrepresented in clinical trials in ALL/ALLy, with those speaking Spanish possibly at a larger disadvantage than those speaking English because some trials lack Spanish informed consent documents. Thus, Spanish‐speaking patients may have been excluded from studies evaluating these regimens, even though census data reports that Hispanics make up the second largest ethnic group after Non‐Hispanic Whites 25,26 . In some pediatric leukemia clinical trials, disparities have been demonstrated in degrees of enrollment as well, with Hispanic and Non‐Hispanic Black patients enrolled to a lesser degree than Non‐Hispanic White patients 25,27 .…”

“… 25 , 26 In some pediatric leukemia clinical trials, disparities have been demonstrated in degrees of enrollment as well, with Hispanic and Non‐Hispanic Black patients enrolled to a lesser degree than Non‐Hispanic White patients. 25 , 27 Winestone et al demonstrated that early mortality was actually decreased among patients enrolled on a clinical trial, compared with those unenrolled. 27 If fewer Spanish‐speaking patients were studied on clinical trials, the mortality risk for Spanish speakers may be secondary to being unenrolled on clinical trials within MHS or from the limited understanding gained from previous clinical trials that may have included fewer Spanish speakers.…”

Racial and ethnic differences in clinical outcomes among patients with multiple myeloma treated with CAR T-cell therapy

“…Likewise, few studies of CAR T-cell therapy in RRMM or other cancer types have investigated racial and ethnic differences in adverse events and outcomes in the SOC setting. 15 , 16 , 19 , 20 , 21 To address this limitation, the goal of this study was to evaluate the safety and efficacy of ide-cel by race and ethnicity among patients with RRMM treated with SOC CAR T-cell therapy. To the best of our knowledge, this is the first investigation of potential racial and ethnic differences among recipients of SOC ide-cel CAR T-cell therapy for RRMM.…”