Children from historically marginalized populations who have been diagnosed with acute lymphoblastic leukemia (ALL) relapse and die more often than those from advantaged households. The front-line therapy for ALL is a two-year regimen that includes adherence to home oral chemotherapy and frequent physician dose-adjustment for blood counts, factors which may contribute to the disparity in outcomes. In contrast, chimeric antigen receptor (CAR) T-cell therapy is administered as a single infusion with six weeks of follow-up care.
New data indicate that children who successfully received CAR T-cell therapy experience equivalent levels of complete remission (CR) and overall survival (OS) regardless of proxied socioeconomic status. Haley Newman, MD, of Children’s Hospital of Philadelphia, and colleagues published their findings in Blood and suggested that CAR T-cell therapy could potentially overcome factors influencing disparate outcomes observed for children with ALL in other treatment settings.
The single-center (tertiary care) study included patients with relapsed or refractory leukemia treated with CD19-directed CAR T cells (CTL019, huCART19, or tisagenlecleucel). The study included 206 patients with a median age of 12.5 years (range 1.4-29.1). The investigators defined poverty-exposure as Medicaid-only insurance and used the Childhood Opportunity Index (COI) to define low neighborhood opportunity at the census tract level. The researchers observed a difference in disease burden at the time of referral for CAR T-cell infusion such that children from more advantaged households were significantly more likely to present with high disease burden (38% with a high disease burden) than were patients exposed to low-opportunity neighborhoods (30% with high disease burden).
The investigators documented a CR rate of 93% for all children in the study, and they observed no significant differences by household poverty (p=0.334) or neighborhood opportunity (p=0.504). Additionally, 36-month OS did not differ significantly by household-poverty exposure (p=0.483): 73.8% for household poverty exposed (95% CI 64.3-84.7) versus 67.7% for household poverty unexposed (95% CI 60.0-76.4). There was also no difference in hazard of death between household poverty exposed and household poverty unexposed populations (p=0.545, adjusted hazard ratio [HR] = 1.2, 95% CI 0.6-2.4). The researchers did observe an increased hazard of relapse among patients from low-opportunity neighborhoods as compared to others (p=0.006, adjusted HR=2.3, 95% CI 1.3-4.1). They concluded, however, that since the OS was similar between children in the different neighborhoods, the cohort was salvageable.
Because the data came from a single center, the authors acknowledged their findings cannot be generalized to all CAR T-cell therapy centers. Allison Barz Leahy, MD, a pediatric oncologist at Children’s Hospital of Philadelphia and senior author on the article, described the facility as being highly resourced and able to provide a number of support services to patients. Such help includes insurance specialists and nurse navigators who assist the patient in accessing treatment.
“I truly think that we provide wrap-around services,” Dr. Leahy said, adding that this support helps mitigate disparities.
“We are thrilled with the results,” Dr. Newman said. “Now we need to shift our focus to multidisciplinary investigation and interventions to reduce barriers to access.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
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 [published online ahead of print, 2022 Nov 9]. Blood. doi: 10.1182/blood.2022017866.
Perspectives
Despite major improvements in OS and relapse-free survival (RFS) for children with ALL, socioeconomic disparities persist.1 This is especially important in an era of ever more individualized and costly therapies.2 Unequal access to high-resource therapies, such as CAR T-cell therapy, for relapsed or refractory (R/R) ALL threatens to widen survival disparities for historically marginalized populations.3,4
This study examined socioeconomic disparities in outcomes for children with R/R CD19+-ALL treated with CD19-directed CAR T-cell therapy at a single tertiary care center. Low socioeconomic status (SES) was defined as household-poverty exposure (sole public insurance) and living in a low-opportunity neighborhood (Childhood Opportunity Index <third quintile). Compared to those of low SES, patients unexposed to household-poverty or low-opportunity neighborhoods were more likely to receive CAR T-cell therapy with high disease burden (>25%). Despite this finding, CR rates, defined as M1 marrow at 28 days post CAR T-cell infusion, did not differ by SES measures. OS did not differ by household-poverty (adjusted HR=1.0, 95% CI 0.5-2.0) or neighborhood opportunity (adjusted HR=1.2, 95% CI 0.6-2.4). There was no significant difference in RFS by household-poverty exposure (adjusted HR=0.7, 95% CI=0.4-1.3). However, patients from low-opportunity neighborhoods had significantly higher hazard of relapse compared to those from higher opportunity neighborhoods (adjusted HR=2.3, 95% CI 1.3-4.1).
These results are contrary to several other studies demonstrating differential outcome for high-resource therapies,3,4 which prompts several questions. Foremost, the authors highlighted that patients’ disease status was fundamentally different at referral and relapse, with those in the higher SES groups having worse prognosticators. This suggests potential disparities in who is considered for CAR T-cell therapy, as children of low SES and more severe disease may be less likely to be considered. Additionally, the study only investigated outcomes at a single well-resourced center, which lacks generalizability to other centers. Lastly, the question on access to CAR T-cell therapy remains, as the study cohort included only those who received CAR T-cell therapy.
Nonetheless, the findings of this study are encouraging. CAR T-cell therapy is delivered via a single infusion and does not depend on at-home adherence or provider dose adjustments. Thus, it has potential to ameliorate SES survival disparities and should be considered for patients with R/R CD19+ ALL who present with social challenges that may impede success with other therapies.
Jamie Shoag, MD, MPH
Cleveland Clinic Children’s Hospital
Cleveland, Ohio
References
- Gupta S, Teachey DT, Devidas M, et al. Racial, ethnic, and socioeconomic factors result in disparities in outcome among children with acute lymphoblastic leukemia not fully attenuated by disease prognosticators: a children’s oncology group (COG) study. Blood. 2021;138(Supplement 1):211-211.
- Bach PB. National coverage analysis of CAR-T therapies – policy, evidence, and payment. New Engl J Med. 2018;379(15):1396-1398.
- Bona K, Li Y, Winestone LE, et al. Poverty and targeted immunotherapy: survival in children’s oncology group clinical trials for high-risk neuroblastoma. J Natl Cancer Inst. 2021;113(3):282-291.
- Bona K, Brazauskas R, He N, et al. Neighborhood poverty and pediatric allogeneic hematopoietic cell transplantation outcomes: a CIBMTR analysis. Blood. 2021;137(4):556-568.