Background Brexu-cel is a CD19 CAR T therapy first approved by the FDA in 2021 for adult patients (pts) with R/R B-cell ALL. In the pivotal phase II ZUMA-3 single arm trial, brexu-cel achieved a high rate (71%) of complete remission or complete remission with incomplete hematological recovery (CR/CRi) with a manageable safety profile. Here, we report outcomes of brexu-cel in a broad real-world patient population.

Methods A total of 197 pts with B-cell ALL were infused with brexu-cel and prospectively enrolled between July 2021 and May 2023 in the CIBMTR registry across 67 centers in the US. In this analysis, we included 138 pts with at least one scheduled follow-up at Day 100 and evaluable safety and effectiveness outcomes. Descriptive statistics, Kaplan-Meier estimator and cumulative incidence functions were used to summarize outcomes.

Results Median age was 43 years (range, 19.4-79.4; 19% were age ≥60 years) and 52% were males. Pts had a diverse ethnic background: 50% non-Hispanic White, 28% Hispanic, 11% non-Hispanic Black and 7% non-Hispanic Asian. More than half (55%) of pts had poor cytogenic risk score at diagnosis. Prior to lymphodepletion (LD), the majority of pts had: ECOG performance status of 0 or 1 (80%); at least one clinically significant comorbidity (79%); and Ph-negative disease (64%). Furthermore, 44% had evidence of ≤5% bone marrow blasts; of these (n=49), 65% were MRD negative. Extramedullary disease and CNS involvement was observed in 22% and 10% of pts prior to LD, respectively. As such, based on adapted criteria available in the registry data, 91% of pts in this cohort would have been ineligible for ZUMA-3. Pts received a median of 4 prior lines of therapy (range 1-13); 46% had prior inotuzumab and 58% had prior blinatumomab. One third (35%) had prior allogeneic (allo) stem cell transplant (SCT). Moreover, 41% of pts received bridging therapy prior to LD. Median time from leukapheresis to brexu-cel infusion was 32 days (inter-quartile range [IQR] 27-42)) and median follow-up time was 5.9 months (95% CI: 5.1-6.1) (Table 1).

Overall CR/CRi rate by Day 100 post infusion was 76%; 70% were still in remission at 6 months post initial response (95% CI: 55-80). For those who were not in response before LD, 63% of them converted into a CR/CRi. Relapse free survival at 6 months was 53% (95% CI: 42-62). The overall survival rate at 6 months was 78% (95% CI: 69-84); primary causes of death were primary disease (n=13/32, 41%) and infection (n=7/32, 22%). About one third (31%) of responders received a subsequent allo SCT. High response rates were observed in all pts regardless of age, prior exposure to blinatumomab, allo SCT, or presence of extramedullary disease prior to LD. Grade ≥3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS, ASTCT consensus) occurred in 9% and 24% of pts, respectively (Table 2). Treatment for CRS and/or ICANS consisted mainly of tocilizumab (67%) and corticosteroids (51%). Most of these adverse events were resolved within 3 weeks of infusion (CRS, 94%; ICANS, 80%). Prolonged cytopenia and neutropenia 30 days post infusion was experienced by 42% and 33% of pts, respectively.

Conclusion In this largest-to-date real-world evidence study of brexu-cel in adult pts with B-cell ALL, response and safety outcomes were consistent with findings from ZUMA-3, even with 91% of patients not meeting ZUMA-3 eligibility criteria. Updated data with longer follow-up will be reported at the time of presentation.

*First and second authors are equal contributors

Itani:Kite, a Gilead Company: Current Employment, Other: Travel Support; Gilead Sciences: Current holder of stock options in a privately-held company. Perales:MorphoSys: Consultancy, Honoraria; Equillium: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Exevir: Consultancy, Honoraria; Allogene: Research Funding; Syncopation: Honoraria; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Orcabio: Consultancy, Current equity holder in publicly-traded company, Honoraria; Cidara Therapeutics: Consultancy, Other; Nektar Therapeutics: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Vor Biopharma: Consultancy, Honoraria; NexImmune: Consultancy, Current equity holder in publicly-traded company; Servier: Other; Sellas Life Sciences: Consultancy; Astellas: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Incyte: Consultancy, Honoraria, Research Funding; Miltenyi Biotec: Honoraria; Celgene: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Omeros: Consultancy, Current equity holder in publicly-traded company, Honoraria; Medigene: Consultancy, Other; DSMB: Other; Caribou: Consultancy, Honoraria; Allovir: Consultancy; AbbVie: Consultancy, Honoraria; Adicet: Honoraria; Kite: Consultancy, Honoraria, Research Funding; VectivBio AG: Consultancy, Honoraria. Gergis:Incyte: Honoraria, Other: Travel Support, Speakers Bureau; Thomas Jefferson University: Current Employment; Jazz: Consultancy, Honoraria, Other: Travel Support, Speakers Bureau; Kite, a Gilead Company: Honoraria, Other: Travel Support and other relationship, Speakers Bureau; Gamida: Consultancy, Current equity holder in publicly-traded company; Iovance: Current equity holder in publicly-traded company; Novartis: Honoraria; Astellas: Speakers Bureau. Aribi:Kite, a Gilead Company: Consultancy; Seagen: Consultancy. Hill:Kite/Gilead: Speakers Bureau; March Biosciences: Consultancy. Jain:AbbVie: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Kite/Gilead: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Medisix: Research Funding; Pfizer: Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Cellectis: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Dialectic Therapeutics: Research Funding; Novalgen: Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; ADC Therapeutics: Research Funding; Precision Biosciences: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Loxo Oncology: Research Funding; Beigene: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Mingsight: Research Funding; Fate Therapeutics: Research Funding; Takeda: Research Funding; Aprea Therapeutics: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; TG Therapeutics: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Genentech: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; TransThera Sciences: Research Funding; Newave: Research Funding; Incyte: Research Funding; BMS: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Ipsen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; CareDX: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; MEI Pharma: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Servier: Research Funding. Leonard:Pfizer: Consultancy; Takeda: Consultancy; Adaptive Biotechnologies: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Kite/Gilead: Consultancy. Wang:Kite, a Gilead Company: Current Employment. Hadjivassileva:Kite, a Gilead Company: Current Employment, Current equity holder in publicly-traded company. Nikolaenko:Kite, a Gilead Company: Current Employment, Current equity holder in publicly-traded company, Other; City of Hope: Current Employment; Rafael Pharmaceuticals: Research Funding. Kloos:Kite, a Gilead Company: Current Employment. Abdeldaim:Gilead Sciences: Current holder of stock options in a privately-held company; Kite, a Gilead Company: Current Employment, Other: Travel Support. Dalton:Gilead Sciences: Current holder of stock options in a privately-held company, Other; Bristol Myers Squibb: Current holder of stock options in a privately-held company, Other; Kite, a Gilead Company: Current Employment. Xu:Kite, a Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company. Pasquini:Kite, a Gilead Company: Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Research Funding; Janssen: Research Funding; Kite Brazil: Honoraria. Kebriaei:Pfizer: Consultancy, Honoraria; Jazz: Consultancy, Honoraria.

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2023
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