Session: 906. Outcomes Research: Lymphoid Malignancies Excluding Plasma Cell Disorders: Poster III
Hematology Disease Topics & Pathways:
Research, Lymphoid Leukemias, ALL, Adult, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Real-world evidence, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Study Population, Human
Methods: Adults with R/R B-ALL treated with commercial brexu-cel from 10/01/2021-12/26/2023 were included from the CIBMTR registry. Key subgroups, including prior treatments, lines of therapy (LOT), pre-infusion MRD status, and high-risk features (e.g., aged ≥55 y, ECOG PS ≥2, >50% pre-infusion bone marrow [BM] blasts, comorbidities, and poor cytogenetic risk score), were examined in univariate and multivariate analyses (MVA) for effectiveness and safety outcomes.
Results: A total of 242 pts were included (median FU 7.2 mo); median age 46.8 y (range 18.5-84.3), 8% <26 y, 35% ≥55 y, 29% Hispanic, 8% ECOG PS ≥2, 81% had comorbidities (30% with moderate/severe pulmonary symptoms at infusion, 10% with history of cardiac comorbidity, and 9% with ongoing infection at infusion [despite a boxed warning in the US label instructing not to administer brexu-cel to pts with active infection or inflammatory disorders]), and 11% had >50% pre-infusion BM blasts (70% had ≤5%). Pts were heavily pretreated, with median 3 prior LOT (interquartile range [IQR], 2-4; 62% blinatumomab [blina]; 44% inotuzumab ozogamicin [InO]) and 32% had prior allogeneic stem cell transplantation (alloSCT; median 25 mo alloSCT to infusion). Pre-infusion CR/CRi rate was 39% (24% MRD negative). Median vein-to-vein time was 32 d (IQR, 27-42) and 50% had bridging therapy.
CR/CRi rate (95% CI) in evaluable pts (n=239) after brexu-cel was 80% (75-85; 68% [60-76] for 145 pts not in CR/CRi pre-infusion). Estimated 6-mo rates (95% CI; n) of duration of remission (DOR), relapse-free survival (RFS), and OS were 67% (58-74; 192; 66% [51-77] in 99 pts not in CR/CRi pre-infusion), 55% (48-62; 242), and 80% (74-84; 242). Of responders, 29% had subsequent alloSCT (median time to alloSCT, 107.5 d [IQR, 84-157]). In MVA, prior blina, InO, and LOT had no significant effectiveness associations. Prior alloSCT was associated with improved DOR (hazard ratio [HR], 0.22 [95% CI, 0.10-0.49]) and RFS (HR, 0.62 [95% CI, 0.40-0.96]). Ongoing infection at infusion was associated with worse CR/CRi (odds ratio [OR], 0.31 [95% CI, 0.10-0.91]), RFS (HR, 1.80 [95% CI, 1.02-3.19]) and OS (HR, 2.67 [95% CI, 1.40-5.10]). There was increased risk of relapse/death for pts not in CR/CRi pre-infusion (HR, 2.08 [95% CI, 1.25-3.45]) vs pts with CR/CRi pre-infusion who were MRD negative.
Rates of any Grade (Gr) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) at 100-d FU were 81% (13% Gr ≥3) and 46% (24% Gr ≥3). Day 30 prolonged thrombocytopenia and neutropenia rates (n=224) were 30% and 34%. Cumulative incidence of infection at 3 mo since infusion was 40%. In MVA, pts with prior alloSCT had higher risk of Gr ≥3 ICANS (OR, 2.25 [95% CI, 1.18-4.27]). Pts with >50% pre-infusion BM blasts had higher risk (OR [95% CI]) of Gr ≥3 CRS (6.39 [2.10-19.47]) and infection (2.14 [1.13-4.05]). Other increased risks (OR) included primary refractory disease with any Gr (8.81) and Gr ≥3 (3.34) CRS; cardiac comorbidity with Gr ≥3 CRS (3.12); aged ≥55 y with any Gr ICANS (4.11); poor cytogenetics with any Gr (1.93) and Gr ≥3 (2.58) ICANS; moderate/severe pulmonary symptoms at infusion with Gr ≥3 ICANS (2.35); not in CR/CRi pre-infusion with prolonged neutropenia (3.78); and 12-24 mo from diagnosis to infusion with prolonged neutropenia (3.32 vs <12 mo) and thrombocytopenia (3.99). Cumulative incidence of non-relapse mortality at 6 mo was 4%.
Conclusions: In the RW, brexu-cel demonstrated high effectiveness and a safety profile consistent with ZUMA-3 in a broader R/R B-ALL pt population than ZUMA-3. Effectiveness was consistent across prior treatments and most high-risk features. Age was not detrimental to safety while some high-risk features, like >50% pre-infusion BM blasts, may require closer monitoring for safety risks.
KW, EB, and YY contributed equally.
Disclosures: Bezerra: Kyverna: Consultancy, Other: Travel, Accomodations, Expenses Support; Kite: Consultancy, Other: Travel, Accomodations, Expenses Support; Novartis: Consultancy. Perales: Syncopation: Consultancy; Astellas: Honoraria; OrcaBio: Consultancy, Current holder of stock options in a privately-held company; Incyte: Consultancy, Honoraria, Research Funding; VectivBio AG: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria, Research Funding; AbbVie: Honoraria; Nektar Therapeutics: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Research Funding; Omeros: Consultancy, Current equity holder in publicly-traded company; Cidara Therapeutics: Other: DSMB member; Karyopharm: Honoraria; MorphoSys: Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Honoraria; Allovir: Consultancy; Allogene: Consultancy, Research Funding; Adicet: Consultancy; Caribou Biosciences: Consultancy; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy; Sellas: Other: DSMB member; Vor Biopharma: Consultancy; Medigene: Other: DSMB member; Servier: Other: DSMB member. Jain: Fate Therapeutics: Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Other: Travel Support, Research Funding; Medisix: Research Funding; Takeda: Research Funding; Aprea Therapeutics: Research Funding; Loxo Oncology: Research Funding; TG Therapeutics: Consultancy, Honoraria, Other: Travel Support; Precision Biosciences: Consultancy, Honoraria, Other: Travel Support, Research Funding; Pfizer: Research Funding; Janssen: Consultancy, Honoraria, Other: Travel Support; Cellectis: Consultancy, Honoraria, Other: Travel Support, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel Support, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding; MEI Pharma: Consultancy, Honoraria, Other: Travel Support; NovalGen: Research Funding; BeiGene: Consultancy, Honoraria, Other: Travel Support; Dialectic Therapeutics: Research Funding; Newave: Research Funding; TransThera Sciences: Research Funding; ADC Therapeutics: Research Funding; CareDx: Consultancy, Honoraria, Other: Travel Support; Ipsen: Consultancy, Honoraria, Other: Travel Support; Servier: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel Support, Research Funding; Incyte: Research Funding; MingSight: Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Other: Travel Support, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Other: Travel Support, Research Funding; AbbVie: Consultancy, Honoraria, Other: Travel Support, Research Funding. Gergis: VOR: Consultancy; Astellas: Other: Travel Support, Speakers Bureau; Biontech: Current equity holder in publicly-traded company; Jazz: Other: Travel Support, Speakers Bureau; Incyte: Other: Travel Support, Speakers Bureau; Kite: Other: Travel Support, Speakers Bureau; Autolus: Consultancy; Moderna: Current equity holder in publicly-traded company; Iovance: Current equity holder in publicly-traded company. Aribi: Kite, a Gilead Company: Consultancy; Seagen: Consultancy. Hill: Kite, a Gilead Company: Speakers Bureau; Gilead Sciences: Speakers Bureau; March Biosciences: Consultancy. Leonard: Adaptive Biotechnologies: Consultancy, Honoraria, Other: Travel, accommodations, and expenses; Pfizer: Consultancy, Honoraria; Kite/Gilead: Consultancy; Takeda: Consultancy; France Foundation: Honoraria. Lutfi: ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees. Hu: Gilead Sciences: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment. Wang: Kite, a Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company. Siddiqi: Amgen: Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months; Kite, a Gilead Company: Current Employment, Other: Travel Support; Gilead Sciences: Current equity holder in publicly-traded company. Damico Khalid: Kite, a Gilead Company: Current Employment, Current equity holder in publicly-traded company, Other: Travel Support. Speiser: Kite, a Gilead Company: Current Employment. Pasquini: Janssen: Research Funding; Novartis: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Kite, a Gilead Company: Honoraria, Research Funding. Kebriaei: Jazz Pharmaceuticals: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Muffly: Bristol Myers Squibb: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Vor: Consultancy, Research Funding; Autolus: Consultancy; Wugen: Research Funding; Jasper: Research Funding; Astellas: Consultancy; Pfizer: Consultancy; Adaptive: Research Funding; Cargo Therapeutics: Consultancy.
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