The impact of race, ethnicity, and obesity on CAR T-cell therapy outcomes.
Aiman J FaruqiJohn A LigonPaul BorgmanSeth M SteinbergToni FoleyLauren LittleCrystal L MackallDaniel W LeeTerry J FryHaneen ShalabiJennifer BrudnoBonnie YatesLekha MikkilineniJames KochenderferNirali N ShahPublished in: Blood advances (2022)
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 5 phase 1 clinical trials at the National Cancer Institute 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 with White non-Hispanic patients even after adjusting for leukemia disease burden and age (odds ratio, 4.5; P = .001). A descriptive analysis of patients with multiple myeloma (n = 24) and non-Hodgkin lymphoma (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.
Keyphrases
- cell therapy
- end stage renal disease
- acute lymphoblastic leukemia
- body mass index
- ejection fraction
- newly diagnosed
- weight loss
- stem cells
- metabolic syndrome
- chronic kidney disease
- clinical trial
- peritoneal dialysis
- mesenchymal stem cells
- type diabetes
- multiple myeloma
- prognostic factors
- oxidative stress
- weight gain
- adipose tissue
- physical activity
- acute myeloid leukemia
- squamous cell carcinoma
- systemic lupus erythematosus
- risk factors
- skeletal muscle
- radiation therapy
- hodgkin lymphoma
- open label
- obese patients
- papillary thyroid