Underprivileged children who receive CAR T-cell therapy for acute lymphoblastic leukemia (ALL) have similar outcomes as those from more advantaged households, according to a new study published in Blood. This is particularly surprising since, overall, children with ALL living in poverty are significantly more likely to relapse and die from early disease than those from wealthier backgrounds.
“What we see here is that among this cohort, CAR T-cell therapy is equally effective regardless of poverty exposure,” said Haley Newman, MD, a fellow in pediatric oncology in the division of oncology and cancer immunotherapy program at Children’s Hospital of Philadelphia (CHOP). “This study suggests that CAR T-cell therapies work equivalently.”
CAR T-cell immunotherapy involves removing a patient’s T-cells, genetically modifying them in a laboratory to target cancer cells, and then infusing them back into the patient’s bloodstream. This therapy has been shown to be successful in improving outcomes for multiple cancers, including ALL in children.
Because social determinants of health affect the outcomes of many illnesses, researchers wondered whether children who lived in poverty would do as well with CAR T-cell treatment as their wealthier peers. The conditions most commonly associated with poverty in the US are diet-related, such as obesity and diabetes. But there is growing evidence that diet can have an effect in health outcomes of cancer treatments, including those of the head and neck and pancreas.
Also, CAR T-cell therapy is particularly taxing. The Dana Farber Cancer Center says: “Patients who receive CAR T-cell therapy have a risk/recovery period of approximately 2-3 months. … It is not uncommon for patients to be admitted to the hospital during this period to manage complications.”
Newman and colleagues studied the outcomes of 206 children and young adults treated at CHOP, with a median age of 12.5 years with reduced/refractory ALL treated on one of five CD19-directed CAR T-cell clinical trials or with a commercial CAR-T, tisagenlecleucel.
They collected data from CAR T-cell clinical trial datasets and electronic medical records from patients treated between April of 2012 and December of 2020. Researchers then sorted patients by socioeconomic and neighborhood opportunity exposures, which they determined using insurance types and patient addresses.
The team considered children with public insurance plans poverty exposed, as compared to those with private or commercial insurances. Medicaid does cover CAR T-cell therapy, which costs about $475,000 per treatment course.
In this study, researchers used a “census tract-based multidimensional quality measure” to determine a household’s access to resources that influence children’s health and development, based on the neighborhood where patients lived.
“Many previous neighborhood studies have sorted data at the zip code level. We actually had address data for these patients, which allowed us to geocode their census tract, which is the level at which the childhood opportunity index is measured,” explained Newman.
The researchers found no significant difference in overall survival or complete remission rates between patients with lower neighborhood health opportunity and those from more advantaged households.
Interestingly, the researchers found that children from more advantaged households were significantly more likely to present with high disease burden at the time of referral for CAR T-cell infusion. Because high-disease burden is associated with inferior outcomes and greater risks for toxicity, those presenting with severe forms of disease are generally considered at greater risk with CAR T-cell treatment.
The team does not have an explanation for this trend. But Allison Barz Leahy, senior author and an oncologist in the division of oncology at CHOP, explains that patients with higher disease burdens from more advantaged households might be referred for CAR T-cell therapy at higher rates than those from lower socioeconomic groups.
The main message of this study, Newman said, is that more children should have access to this treatment whenever they need it. “This study shows us that patients from disadvantaged households do well with CAR T-cell therapy. To me, that says that we need to make this therapy more accessible, whether that be through new interventions, or providing more resources for families, like transportation and funding for medical leave.”
