Although socioeconomic status often influences survival outcomes, pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL) who were living in poverty and were treated with CAR T-cell therapy achieved similar overall survival and were equally likely to achieve a complete response as pediatric patients from more socioeconomically advantaged households, according to a new study published by Newman et al in Blood.

Study Background and Methodology

Previously, some researchers have argued that because marginalized groups have lower overall survival rates, they may be less likely to fare well with CAR T-cell therapy. Patients with pediatric ALL from impoverished backgrounds are significantly more likely to experience relapse and die from their disease than those from wealthier backgrounds, yet CAR T-cell therapy has been shown to successfully improve outcomes for those with the disease. Despite this, the therapy can be expensive, time-intensive, and largely out of reach for many marginalized groups.

“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 hematology and oncology in the Division of Oncology and the Cancer Immunotherapy Program at the Children’s Hospital of Philadelphia. “This study suggests that CAR T-cell therapies work equivalently.”

Study Details

Dr. Newman and her colleagues studied the outcomes of 206 pediatric and young adult patients with a median age of 12.5 years who had relapsed or refractory ALL and were treated in one of five CD19-directed CAR T-cell clinical trials or with the commercial CAR T-cell therapy tisagenlecleucel. They collected data from CAR T-cell clinical trial datasets and electronic medical records from patients treated between April 2012 and December 2020, and then sorted the patients by socioeconomic and neighborhood opportunity exposures.

Pediatric patients with public insurance plans were considered household-poverty exposed, while those with private or commercial insurances were not. Researchers used a census tract-based multidimensional quality measure of U.S. neighborhood metrics to determine neighborhood opportunity and the access a household has to resources that influence children’s health and development.

“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 Dr. Newman.

Findings

The study results revealed no significant differences in the overall survival or complete remission rates between household-poverty exposed patients with a lower neighborhood opportunity and those from more advantaged households—individuals who were unexposed to household poverty or living in high-opportunity neighborhoods.

Interestingly, the data also demonstrated 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 worse outcomes and higher chances for toxicity, those presenting with severe forms of disease are generally considered at greater risk when receiving CAR T-cell treatment.

“We can’t say exactly why we’re seeing a difference in disease burden, but it could be due to provider referral biases, families from more advantaged households having more resources to access CAR-T and more flexibility to take time off work for treatments, or there may be a difference in how families are able to advocate for their children to receive this therapy,” explained Allison Barz Leahy, MD, an oncologist in the Division of Oncology and the Cancer Immunotherapy Program at the Children’s Hospital of Philadelphia, and Assistant Professor in the Department of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania.

Dr. Leahy further explained that although researchers knew that patients with higher disease burdens were generally sicker, the data suggested that those from more advantaged households with high disease burdens were still being referred for CAR T-cell therapy, while those from lower socioeconomic groups were potentially not receiving referrals or were experiencing more challenges when advocating for the same treatment.

While these results provided both hope and evidence to increase access to CAR T-cell therapy for those from disadvantaged households, investigators still voiced the importance of replicating these findings in larger populations outside of clinical trial settings. Dr. Newman and her colleagues noted that this study incorporated data from a single center, so its results could not be generalized to populations outside of the Children’s Hospital of Philadelphia community.

“This study shows us that patients from disadvantaged households do well with CAR T-cell therapy,” concluded Dr. Newman. “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,” she suggested.

Disclosure: For full disclosures of the study authors, visit ashpublications.org.