Background: Chimeric antigen receptor T-cell (CAR T) therapy has transformed the treatment landscape for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and multiple myeloma (MM). However, access to CAR T therapy remains variable across academic and community practices in the US. Utilization, referral patterns, and timelines of CAR T therapy in real-world (RW) settings remain poorly characterized. Understanding how care settings impact access and outcomes is critical to identifying barriers and guiding equitable delivery models.Methods: This longitudinal, retrospective cohort study used patient-level data from the US-based Flatiron Health Research Database, an electronic health record-derived database, which includes structured and unstructured data from academic and community oncology practices across the US. Adults with a CAR T-indicated diagnosis on or after January 1, 2017, were included in a pan-hematologic cohort, using machine learning models to identify CAR T receipt. Disease-specific cohorts (DLBCL, MCL, MM) were curated to include patients treated with commercial (non-trial) CAR T, using technology-enabled human abstraction and quality assurance. We assessed CAR T utilization rates (referral and administration); treatment setting (academic vs community); site-level patient composition, including geocoded socioeconomic status (SES); referral pathways; timelines from decision to infusion (brain-to-vein [B2V]) and from apheresis to infusion (vein-to-vein [V2V]); bridging therapies; and RW overall survival (rwOS).Results: Among 205,858 patients with a CAR T-indicated diagnosis, 7,959 received CAR T therapy. CAR T uptake increased annually by 1.1 per 100 diagnoses (95% confidence interval [CI]: 0.74-1.45), rising from 0.7 per 100 diagnosis in 2017 to 11.1 in 2025, with academic centers demonstrating a higher rate of uptake.

In the disease-specific CAR T cohorts, 1,600 DLBCL, 187 MCL, and 733 MM patients were identified. Over half of patients received some or all of their care at community sites. CAR T was administered at community sites in 19% of DLBCL, 23% of MCL, and 11% of MM cases. Notably, community-based CAR T administration increased over time—from 4% in 2018 to 20% in 2024. The remainder received CAR T at academic centers.

Of 118 community sites, 38 (32%) administered CAR T and 80 (68%) referral-only and had similar patient composition (race, insurance, census-tract-level SES). The highest proportions of CAR T administering sites were observed in the South (42%) and Midwest (21%), with referral-only sites more evenly distributed across regions.

Median (interquartile range [IQR]) B2V and V2V days were 73 (55-99) and 35 (28-43) for DLBCL, 70 (54-99) and 31 (28-39) for MCL, 119 (84-222) and 53 (45-65) days for MM, respectively. No clinically meaningful differences in B2V or V2V days were seen across care settings overall; V2V days were lower in the academic setting for DLBCL (34 vs 36 days) and MCL (30 vs 38 days). In DLBCL, B2V times increased from 61 days in 2018 to 77 days in 2024 .

Bridging therapy was used in the majority of CAR T treated patients: 67% in DLBCL, 70% in MCL, and 75% in MM. Bridging usage increased over time, from 56% in 2018 to 77% in 2024 for DLBCL, 62% in 2021 to 87% in 2024 for MCL, and 61% in 2021 to 78% in 2024 for MM. Use of antibody-drug conjugates in DLBCL and bispecifics in MM increased for bridging, reflecting evolving treatment strategies.

Median rwOS from CAR T infusion was 26.3 (95% CI: 23.6-30.8) months for DLBCL, 37.5 (95% CI: 32.5-NA) months for MCL, and not reached for MM. For DLBCL, rwOS differed significantly over time, from 27.8 months in 2018 to 16.5 months in 2020 and 25.9 months in 2022 (log-rank P = 0.01).Conclusions: In this large RW cohort, CAR T utilization steadily increased, with most patients receiving treatment at academic centers. However, community practices played a substantial and growing role in access, potentially in regions with lower academic site density. While community sites administered a minority of CAR T, B2V and V2V timelines were overall comparable across settings, and bridging therapy use expanded over time. These findings support the feasibility of CAR T delivery across practice types and underscore the need for scalable, regionally adaptive models to ensure equitable access nationwide.

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2025
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