Non-White and Hispanic Patients Have Significantly Longer Time from Intent to CAR T Infusion (“Brain-to-Vein” Time) in Multiply Relapsed Diffuse Large B Cell Lymphoma

Introduction
CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy is an effective treatment for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, CAR-T collection and infusion can be complicated by logistical challenges. Recent studies have explored associations with delays in “brain-to-vein” time (time between initial CAR-T consultation and infusion) with insurance status being a primary factor. However, no studies have explored the relationship between patient race and ethnicity and brain-to-vein time. We sought to determine whether there were differences in brain-to-vein times and outcomes in non-Hispanic White (nH-White) patients versus non-White and Hispanic patients with R/R DLBCL.

Methods
We queried our internal database for all patients who received any CAR-T product as third line or greater treatment for DLBCL between January 1, 2019 and December 31, 2023 at the NYP/Cornell Medical Center. Patient demographics and disease information were collected. Patient race and ethnicity were determined by self-identification in the medical record and defined as either nH-White or non-White (Black, American Indian/Alaska Native, Asian, or Other) and Hispanic/Latino. Insurance status was defined as either public or private. The primary outcome, brain-to-vein time, was time from initial consultation to infusion. Vein-to-vein time, the time from apheresis to infusion, was also determined. Baseline characteristics and times were compared using the Wilcoxon rank sum test. The chi-squared test was used to determine association between race/ethnicity and insurance status. Secondary outcomes included event-free survival (EFS), defined as time to relapse/progression, new treatment, or death, and overall survival (OS), defined as the time from infusion until death. Survival probabilities were compared with long-rank tests.

Results
We identified 80 patients; 52 self-identified as nH-White, and 28 identified as non-White or Hispanic (6 Black, 12 Asian, and 10 of Hispanic/Latino origin). For all patients, median age was 67 (IQR 56-72), 61% had elevated LDH, 6% had an ECOG of >2, and 47% received CAR-T as 4th line or greater, with no significant differences between nH-White and non-white/Hispanic patients. 85% of patients received axicabtagene ciloleucel, 7.5% lisocabtagene maraleucel, and 7.5% tisagenlecleucel.

Non-White and Hispanic patients had longer brain-to-vein times than nH-White patients (median 54 days versus 42 days, p = 0.036). Vein-to-vein times were not statistically different between non-White/Hispanic patients and nH-White patients (median 40 vs 32 days; p = 0.21). Brain-to-vein times were similar for patients with public versus private insurance (p=0.72), and there was no association between race and insurance status (X² = 1.2947, df = 1, p = 0.26). Overall response rates (ORR) and complete response (CR) rates were similar in both groups, with a 68% ORR and 57% with CR in the non-White/Hispanic cohort and a 63% ORR and 46% with CR in nH-White patients. In non-White/Hispanic patients, 1-year OS was 70% (95% CI 53%-92%), median OS was not reached, 1-year EFS was 48% (95% CI 33%-72%), and median EFS was 6 months (95% CI 3 – not reached). In nH-White patients, 1-year OS was 68% (95% CI 56%-83%), median OS was 47 months (95% CI 16 – not reached), 1-year EFS was 37% (95% CI 25%-54%), and median EFS was 7 months (95% CI 4 - 17). There was no significant difference in OS or EFS between groups (p = 0.40 and p = 0.39, respectively).

Conclusion
Non-White/Hispanic patients had significantly longer brain-to-vein times than nH-White patients, though there was no difference in response rates or survival outcomes. Vein-to-vein times were also longer in non-White/Hispanic patients though this was not statistically significant. There was no significant association between race and insurance status and no difference in brain-to-vein times in patients with public versus private insurance. These findings suggest that historically marginalized groups may be at risk for longer wait times for life-saving therapy regardless of insurance status, highlighting the importance of elucidating the social determinants of health that may be contributing. To ensure equitable access to CAR-T cell therapy, larger studies are needed to assess how inequities in health care and social determinants of health result in care delays in at-risk groups.