-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

5092 Real-World (RW) Outcomes for Brexucabtagene Autoleucel (Brexu-Cel) Treatment in Patients (Pts) with Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL) By High-Risk Features and Prior Treatments: Updated Evidence from the CIBMTR® Registry

Program: Oral and Poster Abstracts
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
Monday, December 9, 2024, 6:00 PM-8:00 PM

Kitsada Wudhikarn, MD1, Evandro Bezerra, MD2, Yang Yang, MD3, Miguel-Angel Perales, MD4, Nitin Jain, MD5, Usama Gergis, MD, MBA3, Ahmed Aribi, MD6*, LaQuisa Hill, MD7*, Jessica T. Leonard, MD8, Forat Lutfi, MD9, Soyoung Kim, PhD10*, Matthew Bye, MPH10*, Zhen-Huan Hu, MPH11*, Hai-Lin Wang, MPH12*, Zhong-Cheng Luo, PhD12*, Rubina Siddiqi, PhD12*, Rita Damico Khalid, DO12*, Jessica Speiser, MPH12*, Marcelo C. Pasquini, MD, MS10, Partow Kebriaei, MD5 and Lori Muffly, MD13

1Chulalongkorn University, Bangkok, Thailand
2The Ohio State University, Columbus, OH
3Thomas Jefferson University, Philadelphia, PA
4Memorial Sloan Kettering Cancer Center, New York, NY
5The University of Texas MD Anderson Cancer Center, Houston, TX
6Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
7Baylor College of Medicine, Houston, TX
8Oregon Health & Science University, Portland, OR
9University of Kansas Health System, Kansas City, KS
10Center for International Blood and Marrow Transplant Research, Milwaukee, WI
11Kite Pharma, a Gilead Company, Santa Monica, CA
12Kite, a Gilead Company, Santa Monica, CA
13Stanford University, Stanford, CA

Introduction: Brexu-cel is an autologous anti-CD19 CAR T-cell therapy approved for adults with R/R B-ALL and demonstrated a high complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate (74%) and median overall survival (OS; 25.6 mo; N=78) with >4 y follow-up (FU) in ZUMA-3 (Oluwole et al. ASCO 2024). In a RW study of brexu-cel in pts with R/R B-ALL in the CIBMTR registry (N=150; median FU 6.1 mo), CR/CRi and 6-mo OS rates were both 79%, with safety outcomes consistent with ZUMA-3 (Bezerra et al. ASH 2023). Here, we report updated RW outcomes with longer FU and more pts with key subgroups described.

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.

Previous Abstract | Next Abstract >>
*signifies non-member of ASH