Background

Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR-T) cell therapy that recently received U.S. FDA approval as the first CAR-T cell therapy for adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Social determinants of health (SDoH) are shown to significantly influence outcomes in B-ALL. However, how SDoH relate to and affect outcomes in patients with B-ALL receiving CAR-T therapy has not been well established. We studied the impact of SDoH on outcomes of adults with B-ALL receiving brexu-cel as part of the Real-world Outcomes Collaborative of CAR-T in Adult ALL (ROCCA).

Methods

This retrospective multicenter analysis spanning 25 U.S centers included adults (≥18 years) with r/r B-ALL treated with commercial brexu-cel between 2021-2023. Progression-free survival (PFS) and overall survival (OS) were calculated from the day of brexu-cel infusion and were not censored for hematopoietic cell transplant (HCT) or maintenance. Univariate and multivariate Cox proportional hazards models were used to evaluate the association of age, sex, pre-apheresis disease burden, and SDoH (referral source, insurance, distance from home to CAR-T site, marital status, and the social deprivation index) with progression-free survival (PFS) and overall survival (OS). The social deprivation index (SDI), a composite measure (including income, education, employment, housing, household characteristics, and transportation) used to quantify socio-economic variation in health outcomes, with higher SDI indicating greater social disadvantage, was estimated at the zip code level. (Butler et al., 2013)

Results

Of the 152 patients who received brexu-cel (Table 1), 57% were male. 51% identified as non-Hispanic White, with the remainder identifying as Hispanic (34%), Asian/Pacific Islander (7%), Black (6%), American Indian/Alaskan Native (1%), or mixed race (1%). A majority (46%) were referred for brexu-cel from private/community-based practices and 62% lived within 50 miles of the CAR-T center (36% lived >50 miles and 2% were unknown). Health insurance coverage included primarily public (49%) and private (42%); no patients were uninsured. High SDI (76-100% percentile) was present in 26%, while 14% had a low SDI (0-25 th percentile).

In unadjusted analyses, there was no difference in PFS or OS between patients with high versus low SDI; closer distance to the CAR-T site (<50 miles versus >50 miles)) was associated with worse OS (HR 1.96; 95% CI 1.00, 3.84; p=0.05).

Multivariate analysis (Table 2) revealed that male sex was associated with inferior PFS (HR 1.98; 95% CI 1.02, 3.85; p=0.04) and OS (HR 2.52; 95% CI 1.09, 5.84; p=0.03). There was no difference in PFS (HR 0.95, 95% CI 0.48-1.88, p=0.88) or OS (HR 0.80; 95% CI 0.33,1.92; p=0.62) when comparing Hispanic and non-Hispanic White patients. Additionally, there was no difference in PFS or OS based on any SDoH, including insurance type, marital status, referral source, caregiver type, and distance to transplant center.

Conclusions

In patients receiving brexu-cel, survival outcomes appear independent of SDoH. Contrary to previous reports suggesting inferior outcomes for Hispanic patients with B-ALL after receiving traditional systemic therapies, we observed comparable outcomes to non-Hispanic patients treated with brexu-cel. Distance from the CAR-T site and referrals from the community did not affect outcomes. Additionally, those with higher SDI had similar outcomes to those with a lower SDI, although this analysis was limited by sample size and the selection bias that exists in being referred for brexu-cel in the first place. The relatively lower logistical burden of CAR-T compared to allogeneic stem cell transplant or non-fixed duration systemic therapies may have mitigated the impact of SDoH on outcomes. These real-world data suggest that continuing to improve access to and treatment with brexu-cel may improve overall outcomes for disadvantaged populations with r/r B-ALL.

Lin:Biomarin: Current equity holder in publicly-traded company; Rigel Pharmaceuticals: Consultancy. Aldoss:Pfizer: Consultancy; Sobi: Consultancy; KiTE: Consultancy; Amgen: Consultancy, Honoraria; Takeda: Consultancy; Jazz: Consultancy. Faramand:Gilead: Research Funding; Kite: Research Funding. Logan:Amgen, Autolus Therapeutics, Kadmon, Kite, Pharmacyclics, Talaris: Research Funding; AbbVie, Amgen, Actinium, BMS, Pfizer, Sanofi, Takeda: Consultancy. Schwartz:Jazz Pharmaceuticals: Consultancy; Novartis: Consultancy. Battiwalla:Fate Therapeutics: Research Funding; Novartis: Research Funding. Shaughnessy:BMS: Speakers Bureau; Sanofi: Speakers Bureau. Advani:Nkarta: Honoraria; Pfizer: Honoraria, Research Funding; Amgen: Honoraria, Other: advisory board, Research Funding; Taiho: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Kite: Honoraria, Other: consulting, Research Funding; Glycomimetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunogen: Research Funding; Beam: Honoraria; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kura: Honoraria; Servier: Research Funding; Macrogenics: Research Funding; Seattle Genetics: Research Funding; OBI: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hoeg:Orca Bio: Research Funding. Solh:Bristol-Myers Squibb: Speakers Bureau. Lee:BMS: Honoraria; Kadmon: Honoraria; Kite Pharma: Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria; Fresenius Kabi: Consultancy; Incyte Corp: Consultancy, Research Funding. Kota:Incyte: Research Funding; Kite: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Koura:BMS: Consultancy, Research Funding. Leonard:Pfizer: Consultancy; Adaptive Biotechnologies: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Takeda: Consultancy; Kite/Gilead: Consultancy. Oliai:Jazz Pharmaceuticals: Research Funding; Pfizer: Research Funding; Seagen: Research Funding; Arog: Research Funding; Novartis: Research Funding; Orca Bio: Research Funding. Bachanova:ADC: Membership on an entity's Board of Directors or advisory committees; Allogene: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Citius: Research Funding; Incyte: Research Funding; Gamida Cell: Research Funding; Miltenyi: Other: DSMB. Stock:Amgen: Honoraria; Kite: Consultancy; Kura: Research Funding; Servier: Other: Data Safety Monitoring Board/Advisory Board; Newave: Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria; Glaxo Smith Kline: Consultancy. Cassaday:Vanda Pharmaceuticals: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Kite/Gilead: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Incyte: Research Funding; Servier: Research Funding; Jazz: Consultancy, Honoraria; Autolus: Membership on an entity's Board of Directors or advisory committees; PeproMene Bio: Membership on an entity's Board of Directors or advisory committees; Seagen: Other: Spouse was employed by and owned stock in Seagen within the last 24 months.. Shah:Moffitt Cancer Center: Current Employment; DSMC, Pepromene Bio: Membership on an entity's Board of Directors or advisory committees; Incyte, Jazz Pharmaceuticals, Kite/Gilead, SERVIER: Research Funding; Pharmacyclics/Janssen, Spectrum/Acrotech, BeiGene, Gilead Sciences: Honoraria; Celgene, Novartis, Pfizer, Janssen, Seattle Genetics, AstraZeneca, Stemline Therapeutics, Kite/Gilead: Other: Travel, Accommodations, Expenses; Takeda, AstraZeneca, Adaptive Biotechnologies, BMS/Celgene, Novartis, Pfizer, Amgen, Precision Biosciences, Kite/Gilead, Jazz Pharmaceuticals, Century Therapeutics, Deciphera, Autolus Therapeutics, Lilly, Pepromene: Consultancy. Muffly:amgen: Consultancy; adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; kite: Consultancy, Honoraria, Research Funding; orca bio: Research Funding; bms: Research Funding; autolus: Consultancy; astellas: Consultancy, Research Funding; pfizer: Consultancy; jasper: Research Funding. Tsai:Jazz Pharmaceutical: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Dholaria:Pluri Biotech: Consultancy; AstraZeneca: Research Funding; Atara: Research Funding; MEI: Research Funding; Poseida: Research Funding; NCI: Research Funding; Orca Bio: Research Funding; Allovir: Research Funding; Boxer Capital: Consultancy; Adicet: Research Funding; Angiocrine: Research Funding; Molecular Templates: Research Funding; Lumanity: Consultancy; Ellipsis pharma: Consultancy; Takeda: Research Funding; Arivan: Consultancy; ADC therapeutics: Consultancy, Honoraria; Gilead: Research Funding; Wugen: Research Funding; Pfizer: Research Funding; BEAM therapeutics: Consultancy; gamida cel: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; BMS: Research Funding; Poseida: Research Funding.

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2023
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