CAR-T Outcome Measures Unaffected by Socioeconomic Status and Neighborhood Opportunity

Overall survival (OS) and complete remission (CR) rates are not affected by socioeconomic status and neighborhood opportunity proxy measures for young patients who receive CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma, according to a study recently published in Blood.¹

A retrospective analysis of 206 patients aged between 1.4 and 29.1 years who received CAR-T therapy at Children’s Hospital of Philadelphia (CHOP) identified 35.9% of the included patients as household-poverty exposed, using Medicaid-only insurance as a proxy, and 24.9% as having low neighborhood opportunity, defined by the Childhood Opportunity Index using the patients’ electronic medical record-abstracted home addresses. It was found that the CR rate for the whole cohort was 93%, with no significant differences based on household-poverty (P = .334) or neighborhood opportunity (P = .504). In terms of hazard of death, there was also no significant difference based on neighborhood opportunity (P = .545, adjusted hazard rate [HR], 1.2 [95% CI, 0.6-2.4]) and household-poverty (P = .971, adjusted [HR], 1.0 [95% CI, 0.5-2.0]) in multivariate analyses. However, it was noted that patients identified as having low neighborhood opportunity had an elevated hazard of relapse compared to other patients in a multivariate analysis (P = .006, adjusted HR, 2.3 [95% CI, 1.3-4.1]).

“This study shows us that patients from disadvantaged households do well with CAR T-cell therapy,” first author Haley Newman, MD, a pediatric oncology fellow in the Cancer Center and Cancer Immunotherapy Program at CHOP, said in a statement regarding the study’s publication.² “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.”

The study examined records from patients treated from 2012 to 2020.¹ Included patients had a median age of 12.5 years and had received either investigational CTL019/tisagenlecleucel (62.14%), commercial Kymriah (21.84%), or huCART19 (16.02%). The median follow-up was 46 months overall, 48 months for patients who were household-poverty unexposed, 43 months for those who were household-poverty exposed, 48 months for those who were from high-opportunity neighborhoods, and 39 months for those who were from low opportunity neighborhoods. As such, the investigators censored survival times at 39 months. The analysis included patients from Puerto Rico and 38 different states in the United States. Patients with addresses that could not be geocoded (n=5) were not included in the neighborhood-level analysis. Household-poverty exposure varied by patient race, with 60% of black patients, 70% of Hispanic patients, and 23% of non-Hispanic white patients being household-poverty exposed. It was noted that only 60% of patients with low-neighborhood opportunity were household-poverty exposed, and 27% of patients from high-opportunity neighborhoods were household-poverty exposed.  

“We observed an increased hazard of relapse among patients from low opportunity neighborhoods, although OS was similar, potentially suggesting superior salvageability in this cohort,” Newman and colleagues noted in the paper.¹ “This may be related to CD19 status: low-neighborhood opportunity patients were more likely to experience CD19+ relapse when compared to high-neighborhood opportunity relapsed patients, possibly attributable to lower disease burden at infusion among low-neighborhood opportunity patients, as CD19 positivity allows for salvage with additional CD19-targeted agents. This increased hazard of relapse was not observed among household-poverty exposed patients.”

An additional important finding highlighted by the investigators was the greater likelihood of patients who were household-poverty exposed (P = .010) and from neighborhoods with low opportunity (P = .049) to receive CAR-T while presenting with lower marrow disease burden compared to the patients who were not household-poverty exposed or from neighborhoods with low opportunity. The investigators suggested that this disparity could be due to a bias in access or referral patterns causing patients from disadvantaged households and neighborhoods being less likely to be referred for CAR-T treatment when they have higher disease burden, at which point CAR-T therapy is associated with inferior outcomes and carries a greater risk of toxicity.

Newman and colleagues noted several limitations of their study, pointing out that it only included patients treated at CHOP and only included 15 black patients (7.28%). They also highlighted the fact that the proxy used for socioeconomic status may have led to misclassification for some patients, especially patients from higher income homes whose parents may have recently switched to Medicaid-only insurance as a result of the patient’s cancer. The investigators also noted that the inclusion of many patients who received investigational therapies could affect generalizability to commercial treatments. They concluded that further research is needed to confirm the study’s findings, pointing out that studies incorporating self-reported income and self-reported social determinants of health are particularly necessary.

REFERENCE

1. Newman H, Li Y, Liu H, et al. Impact of poverty and neighborhood opportunity on outcomes for children treated with CD19-directed CAR T-cell therapy. Blood. Published online November 9, 2022:blood.2022017866. doi: 10.1182/blood.2022017866

2. CHOP Study finds CAR T-cell therapy improves survival regardless of socioeconomic status. News release. Children’s Hospital of Philadelphia. November 10, 2022. https://www.chop.edu/news/chop-study-finds-car-t-cell-therapy-improves-survival-regardless-socioeconomic-status