10511 Background: CNS relapse of B-ALL is difficult to treat after cranial radiation or multiple relapses. Durable remissions of relapsed/refractory (r/r) B-ALL have been seen with CD19 CAR T cells; however, most trials excluded patients with active CNS disease. As we observed CAR trafficking into the CSF, we hypothesized that CD19 CAR T cells could control CNS B-ALL. Methods: We identified children and young adults with r/r CNS B-ALL treated on 4 clinical trials of CD19 CAR T cells, CTL019 or CTL119. NCT01626495 and NCT02435849 excluded active CNS disease, while the former in an amendment as well as NCT02374333 and NCT02906371 permitted active CNS disease controlled on therapy. All trials permitted CNS disease that cleared and excluded bulky intracranial disease that did not improve. We analyzed outcomes (CR, RFS) and safety. Results: We identified 65 patients 1-29y (median 10y) with r/r CNS B-ALL (CNS+) of 182 treated with CTL019/CTL119. There were no differences in age, sex, history of SCT or neurologic comorbidities in the CNS+ and CNS- cohorts. CNS+ patients were more likely to be in ≥2nd relapse (74% vs 46%, p < 0.01), to have received cranial radiation (58% vs 11%, p < 0.01), to have detectable CNS disease (p = 0.02) and less bone marrow disease pre-infusion (p < 0.01). At 1 mo post infusion, 62 (95%) CNS+ and 110 (94%) CNS- patients were in CR; 1 in each cohort died of sequelae of CRS and was inevaluable for response. All patients with CNS disease detected pre-infusion cleared by mo 3, including 9 in the CNS+ cohort [5 CNS2 ( < 5 CSF WBC with blasts), 4 CNS3 ( > 5 CSF WBC with blasts or exam/imaging evidence)] and 8 in the CNS- cohort (isolated CNS2 status pre-infusion). There was no difference in RFS (p = 0.28) in the CNS+ and CNS- cohorts [24-mo RFS: 61% (95% CI 46-73%) and 60% (95% CI 48-70%)]. There were 4 CNS relapses in the CNS+ cohort, and 1 in the CNS- cohort. Encephalopathy rate and grade was similar in the CNS+ and CNS- cohorts (52% vs 40% any grade; 12% vs 11% grade 3/4; p = 0.41). There were no deaths due to neurotoxicity (NT) and no statistically significant differences in incidence or severity of any NT or CRS in the CNS+ and CNS- cohorts. Conclusions: The CD19 CAR T cell therapies CTL019/CTL119 are effective at clearing CNS disease and inducing durable remissions in children and young adults with r/r CNS B-ALL. CNS relapse rates are low ( < 3%). Most CD19 CAR T cell trials excluded patients with active CNS disease, primarily due to the risk of NT. We show that patients with r/r CNS B-ALL that is adequately controlled prior to infusion can be safely treated with CD19 CAR T cells, with no increased risk of NT. Clinical trial information: NCT01626495, NCT02435849, NCT02374333, NCT02906371.
7013 Background: CD19-directed chimeric antigen receptor T cell (CART) therapy has dramatically improved survival for children with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). While significant socioeconomic (SES) outcome disparities exist for children with newly diagnosed B-ALL, the impact of SES on CART access and outcomes is poorly described. Using the largest single-center pediatric CART experience, we investigated the hypothesis that poverty-exposed children would have inferior survival outcomes compared to unexposed children. Methods: Retrospective cohort study of US pediatric patients treated on CD19 CART clinical trials or with commercial tisagenlecleucel at Children's Hospital of Philadelphia from 2012-2020. Poverty was the primary exposure, defined at the household-level by insurance status (public vs private). Neighborhood opportunity was defined by census-derived Childhood Opportunity Index (COI) (low [q1-2] vs high [q3-4]). Overall survival (OS) and relapse-free survival (RFS) were evaluated by Kaplan Meier methods, and association with exposures by Cox regression models. Results: Among 206 patients, 36% were household poverty exposed, 24.9% low COI, 21.4% identified as Hispanic, 7.3% non-Hispanic Black, 63.6% non-Hispanic White, and 7.7% non-Hispanic Other. Household-poverty exposure was similar between local and referred patients (32.4% vs 36.7%). Patients unexposed to poverty at the household level or with high COI presented to CART with high disease burden (37.1% vs 26%, p = 0.049, 37.9% vs. 29.7%, p = 0.002). In multivariate analysis adjusting for age, race/ethnicity, disease burden, relapse status, and inotuzumab exposure, there were no significant differences in OS by householdverty (HR 0.86, 95%CI 0.50-1.48, p = 0.575) or low COI (HR 1.03, 95%CI 0.53-1.99, p = 0.932). Low COI was associated with inferior RFS (HR 2.26, 95%CI 1.34-8.80, p = 0.002). There was no significant difference in RFS by household-poverty (HR 0.84, 95%CI 0.48-1.44, p = 0.520). Conclusions: Household poverty was not associated with inferior survival outcomes in pediatric patients who received CART for r/r B-ALL. Patients with low neighborhood opportunity had increased hazard of relapse, a finding that requires investigation of the COI components underlying this association. Patients of higher proxied SES were more likely to have high disease burden, an access inequity potentially reflecting referral pattern bias or greater ability of advantaged families to advocate for CART. Future institutional and multi-center studies should utilize patient-reported social determinants of health to investigate mechanisms driving these disparities and guide care delivery interventions to improve equity in access and outcomes. Clinical trials: NCT01626495, NCT02435849, NCT02374333, NCT02228096, NCT02906371
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