-Author name in bold denotes the presenting author
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4200 NGS MRD Negativity on Day 28 after Brexu Cel in Adults with R/R ALL Is Associated with Favorable Progression Free Survival

Program: Oral and Poster Abstracts
Session: 613. Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Poster III
Monday, December 9, 2024, 6:00 PM-8:00 PM

Yannis K. Valtis, MD1, David Nemirovsky2*, Sean M. Devlin, PhD2*, Gregory W Roloff, MD3, Ibrahim Aldoss, MD4, Nikeshan Jeyakumar, MD5, Katharine Miller, PhD, MPH6*, Amy Zhang, PhD6*, Katherine C. Sutherland, PA-C7*, Anjali S. Advani, MD8, Marlise R. Luskin, MD9, Evan C. Chen, MD10, Omer Jamy, MD11, Michael R. Grunwald, MD12, Ibrahim Muhsen, MD13, Noam E. Kopmar, MD14, Bhagirathbhai R. Dholaria, MBBS15, Simone E. Dekker, MD, PhD16, Jessica T. Leonard, MD17, George Yaghmour, MD18, Stephanie B. Tsai19, Wendy Stock, MD20, Jozal Moore, MD21, Kristen M. O'Dwyer, MD22, Aaron C. Logan, MD, PhD23, Matthew P Connor, MD24, Noelle Frey, MD, MS25, Evandro Bezerra, MD26, Sumithira Vasu, MD, MBBS27, Kaitlyn C Dykes, MD, BS28, Minoo Battiwalla, MD29, Chenyu Lin, MD30, Matthew Ulrickson, MD31, Ran Reshef, MD, MSc32, Ryan D. Cassaday, MD33, Laquisha C. Hill, MD34, Catherine J. Lee, MD, MSc35, Vamsi K. Kota, MD36, Jacob Boccucci, MD37*, Joshua Sasine, MD38, Akil Merchant, MD39, Vinod Pullarkat, MD40, Amelia Langston, MD41, Talal Hilal, MD42, Rawan Faramand, MD43, Melhem M. Solh, MD44, Tamer Othman, MD45, Timothy E O'Connor, MD19, Navneet Majhail, MD, MS, FASTCT46, Shabaz Malik, MD47*, Luke Mountjoy, DO48, Rasmus T. Hoeg, MD49*, Caspian H. Oliai, MD50, Vishal Gupta, MD51*, Divya Koura, MD52, Muthu V. Kumaran, MD53*, Marc Schwartz, MD54, Veronika Bachanova, MD, PhD55, Sean I. Tracy, MD, PhD56*, Maria Odstrcil Bobillo, MD57*, Abdullah Ladha, MD58*, Clayton Jackson, MD59*, Vivian Irrizary Gatell, MD60*, Olalekan O. Oluwole, MD, MPH, MBBS61, Michael Daunov, DO62, John Mathews, MD63*, Paul Shaughnessy, MD64, Bijal D Shah, MD65, Lori Muffly, MD66 and Jae H. Park, MD67

1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
2Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY
3University of Chicago, Chicago, IL
4Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Duarte Cancer Center, Duarte, CA
5Division of Blood and Marrow Transplantation & Cellular Therapy, Stanford University School of Medicine, Stanford, CA
6Stanford University School of Medicine, Stanford, CA
7Division of Blood and Marrow Transplantation & Cellular Therapy, Stanford University, Stanford
8Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH
9Center for Adult Leukemia, Dana-Farber Cancer Institute, Boston, MA
10Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
11O'Neal Comprehensive Cancer Center at University of Alabama at Birmingham, Birmingham, AL
12Department of Hematologic Oncology and Blood Disorders, Atrium Health Levine Cancer Institute, Charlotte, NC
13Baylor College of Medicine, Houston, TX
14Fred Hutchinson Cancer Center, Seattle, WA
15Vanderbilt University Medical Center, Nashville, TN
16Department of Hematology & Medical Oncology, Oregon Health & Science University, Portland, OR
17Knight Cancer Institute, Oregon Health and Science University, Portland, OR
18USC Norris Comprehensive Cancer Center, Los Angeles, CA
19Loyola University Medical Center, Chicago, IL
20Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL
21Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY
22University of Rochester Medical Center, Rochester, NY
23Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA
24Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA
25University of Pennsylvania, Philadelphia, PA
26Division of Hematology, The Ohio State University, Columbus, OH
27Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, OH
28University of California San Diego, San Diego, CA
29Sarah Cannon Transplant and Cellular Therapy Network, HCA Healthcare, Nashville, TN
30Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC
31Banner/MD Anderson Cancer Center, Gilbert, AZ
32Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY
33University of Washington and Fred Hutchinson Cancer Center, Seattle, WA
34Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital, Houston, TX
35Huntsman Cancer Institute, University of Utah, Mercer Island, WA
36Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA
37Georgia Cancer Center, Augusta University, Augusta, GA
38Cedars-Sinai Medical Center, Los Angeles, CA
39Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA
40City of Hope, La Canada, CA
41Emory University, Winship Cancer Institute, Atlanta, GA
42Division of Hematology and Oncology, Mayo Clinic Arizona, Phoenix, AZ
43Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
44BMT Group of Georgia, Atlanta, GA
45Hematology/HCT, City of Hope, San Lorenzo, CA
46Sarah Cannon Transplant and Cellular Therapy Program at TriStar Centennial Medical Center, Nashville, TN
47Sarah Cannon Transplant and Cellular Therapy Program at St. David’s South Austin Medical Center, Austin, TX
48The Colorado Blood Cancer Institute a part of Sarah Cannon Cancer Institute at Presbyterian/St Luke's Medical Center, Denver, CO
49Comprehensive Cancer Center, University of California, Davis, Sacramento, CA
50Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA
51University of California Los Angeles, Los Angeles
52UCSD Moores Cancer Center, San Diego, CA
53University of Arkansas for Medical Sciences, Little Rock, AR
54Division of Hematology, University of Colorado, Denver, CO
55Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN
56Center for Immunology, Masonic Cancer Center, Division of Hematology Oncology and Transplantation, University of Minnesota, Minneapolis, MN
57Huntsman Cancer Institute, University of Utah, Division of Hematology and Hematologic Malignancies, Salt Lake City, UT
58Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA
59Division of Hematology/Oncology, Department of Internal Medicine, University of Texas Southwestern, Dallas, TX
60Division of Hematology and Oncology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
61Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN
62Department of Hematology and Stem Cell Transplant, University Hospitals Seidman Cancer Center, Cleveland, OH
63Sarah Cannon Transplant and Cellular Therapy Network, HCA Healthcare, Dallas, TX
64Sarah Cannon Transplant and Cellular Therapy Program, Methodist Hospital, San Antonio, TX
65Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL
66Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA
67Cell Therapy Service and Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY

Introduction: Brexucabtagene autoleucel (brexu cel) is a CD19-targeted chimeric antigen receptor (CAR) T cell therapy approved for the treatment of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). Some patients (pts) proceed with a consolidative allogeneic hematopoietic cell transplant (HCT) after breux cel. We do not know which pts can safely avoid a consolidative HCT and its associated morbidity.

Methods: We conducted a retrospective cohort study utilizing the Real-World Outcomes Collaborative of CAR-T in Adult ALL (ROCCA) dataset. ROCCA is a registry of brexu cel pts in 32 centers in North America.

We defined complete remission (CR) as < 5% blasts in the bone marrow and no central nervous system (CNS) or extramedullary (EM) disease on or around D28 after brexu cel. We defined measurable residual disease negative (MRD-) CR as CR and no abnormal blasts in the bone marrow by multiparameter flow cytometry, quantitative polymerase chain reaction, ClonoSeq next generation sequencing (NGS), or other sequencing modalities with lower sensitivity. ClonoSeq NGS has a sensitivity of 10-6, while the other modalities have a sensitivity of at least 10-4. We defined progression free survival (PFS) as the time from CAR-T infusion to relapse or death, censored at the date of last follow-up.

Statistical analyses were performed in R. Univariable Cox proportional hazards regression analyses were performed to determine the association of pre-specified variables with PFS. Variables known to be associated with CAR T outcomes in ALL were entered into a multivariable model. HCT was incorporated as a time-varying covariate.

Results: During the study period, 281 pts were infused with brexu cel. We focused our analysis on 172 (61%) pts with confirmed MRD- CR on D28, as that is the group with clinical equipoise regarding maintenance strategy. 38 (22%) of those pts received a consolidative HCT, 30 (17%) received another form of maintenance therapy (primarily tyrosine kinase inhibitors for Philadelphia (Ph)-chromosome positive ALL), and 104 (60%) pts received no maintenance therapy. Pts who underwent consolidative HCT were younger (median age 35 years) than those who received no maintenance (42y) (p = 0.023) and were less likely to have a history of prior HCT (13% vs. 47%, p < 0.001). No differences were observed with respect to sex, TP53 mutation status, prior inotuzumab (ino) or blinatumomab (blina) exposure, disease burden prior to CAR, or development of any cytokine release syndrome (CRS) or any neurotoxicity with brexu cel.

We performed univariable Cox proportional hazard regression analyses among pts in MRD- CR on D28, excluding those who received other maintenance therapy besides HCT; the median follow up was 8.1 months. In univariable analyses, D28 MRD negativity by ClonoSeq NGS (versus MRD negativity by other, less sensitive methods), development of CRS, and pre-CAR BM blasts < 5% were associated with improved PFS; prior ino exposure was negatively associated with PFS (p < 0.05). Age, sex, Ph status, TP53 status, and neurotoxicity development were not associated with PFS. In a multivariable model incorporating ALL type, prior HCT, prior ino/blina, and pre-CAR blast burden, as well as consolidative HCT as a time-varying covariate, only MRD negativity by ClonoSeq NGS with at least 10-6 sensitivity retained statistical significance (PFS hazard ratio 0.34, 95% confidence interval (CI) 0.15-0.77, p = 0.005).

Pts who were MRD- by ClonoSeq NGS on D28 and received no maintenance had favorable 6m PFS of 76% (95% CI: 59-98%) and OS of 100% with a median follow up of 6.3 months in this subgroup. Among those in MRD- CR by NGS, HCT as a time-varying covariate was not associated with improved PFS (HR 0.6, p = 0.6).

Conclusions: In a large real-world cohort of adults with R/R B-ALL infused with brexu cel, we identified practice variation regarding the use of consolidative HCT. Among brexu cel recipients who entered an MRD- CR, we identified ClonoSeq NGS MRD negativity as a novel predictive factor of favorable oncologic outcomes, even without a consolidative HCT. Similar results have been obtained in pediatric ALL patietns ftreated with 41BB-based tisagenleucleucel (Pulsipher et al., Blood Cancer Discovery 2022). Longer follow-up is needed to validate the safety of omitting consolidative HCT in such pts, but these results encourage the potential for definitive therapy with brexu cel when D28 ClonoSeq NGS MRD is negative.

Disclosures: Valtis: EastRx: Consultancy. Roloff: Kite: Honoraria. Aldoss: Sobi: Other: consulting fees; AbbVie: Other: research support; Pfizer: Honoraria, Other: consulting fees; Kite Pharma: Other: consulting fees; Takeda Pharmaceuticals: Other: consulting fees; Jazz Pharmaceuticals: Other: consulting fees; Syndax Pharmaceuticals, Inc.: Other: consulting fees; Amgen: Honoraria, Other: consulting fees. Sutherland: Orca Bio, Inc.: Consultancy. Advani: Pfizer: Other: Manuscript help, Research Funding; PER: Honoraria; American Society of Hematology: Honoraria; Emmes: Honoraria; MD Education: Honoraria; Springer: Honoraria; Glycomimetics: Research Funding; Wiley: Honoraria; BEAM: Other: Research support, Research Funding; Kura: Research Funding; Wolters Kluwer: Honoraria; Kite: Consultancy, Research Funding; Servier: Research Funding; Macrogenics: Research Funding; MJH Life: Honoraria; Amgen: Research Funding; Immunogen: Research Funding; Incyte: Research Funding; Web MD: Honoraria; Seattle Genetics: Research Funding; OBI: Research Funding; Novartis: Consultancy. Luskin: Pfizer: Honoraria; KITE: Honoraria; Jazz: Honoraria; AbbVie: Research Funding; Novartis: Honoraria, Research Funding. Chen: Rigel: Consultancy; AbbVie: Consultancy. Grunwald: Medtronic: Current holder of stock options in a privately-held company; Merck: Research Funding; Janssen: Research Funding; Ajax: Research Funding; Sobi: Consultancy; Servier: Consultancy; Sanofi: Consultancy; Premier: Consultancy; Pfizer: Consultancy; OncLive: Consultancy; Jazz Pharmaceuticals: Consultancy; Incyte Corporation: Consultancy, Research Funding; GSK: Consultancy; Genetech: Consultancy; Daiichi Sankyo: Consultancy; Cardinal Health: Consultancy; Bristol Myers Squibb: Consultancy; Blueprint Medicines: Consultancy; Astellas Pharma: Consultancy; Aptitude Health: Consultancy; Amgen: Consultancy. Dholaria: Janssen, Angiocrine, Pfizer, Poseida, MEI, Orcabio, Wugen, Allovir, Adicet, BMS, Molecular template, Atara: Research Funding; MJH BioScience, Arivan Research, Janssen, ADC therapeutics, Gilead, GSK, Caribou, Roche, Autolus, Sanofi.: Consultancy, Honoraria. Leonard: France Foundation: Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria, Other: Travel, accommodations, and expenses; Pfizer: Consultancy, Honoraria; Takeda: Consultancy; Kite/Gilead: Consultancy. Yaghmour: USC Keck School of Medicine: Current Employment; Pharmacyclics: Research Funding; Abbvie: Other: Advisory Board; Daiichi: Other: Advisory Board; Astazeneca: Other: Advisory Board; GSK: Speakers Bureau; Rigel: Speakers Bureau; Servier: Speakers Bureau; Jazz: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Kite: Speakers Bureau; SOBI: Speakers Bureau; Incyte: Speakers Bureau; Secura Bio: Speakers Bureau; Astellas: Speakers Bureau; Blueprint: Speakers Bureau; ABBVie: Speakers Bureau; Stemline therapeutic: Speakers Bureau; Alexion: Other: consult. Tsai: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Jazz, Sanofi: Honoraria. Stock: Kura, Servier, Newave, Adaptive, Jazz, Asofarma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Adaptive: Consultancy, Honoraria. Logan: Talaris: Research Funding; Sanofi: Consultancy; Pfizer: Consultancy; Autolus: Research Funding; Takeda: Consultancy; Actinium: Consultancy; Pharmacyclics: Research Funding; Kadmon/Sanofi: Research Funding; Bristol Myers Squibb: Consultancy; Kite: Consultancy; Kite/Gilead: Research Funding; AbbVie: Consultancy; Amgen: Consultancy, Research Funding; Astellas Pharma: Research Funding. Frey: Kite Pharma: Consultancy; Autolus: Consultancy. Bezerra: Kite: Consultancy, Other: Travel, Accomodations, Expenses Support; Kyverna: Consultancy, Other: Travel, Accomodations, Expenses Support; Novartis: Consultancy. Vasu: Alexion Inc: Speakers Bureau; Sanofi: Research Funding. Battiwalla: Kite/Gilead: Research Funding; Astra Zeneca/Gracell: Research Funding; JNJ/Janssen: Research Funding; Fate Therapeutics: Research Funding. Lin: Autolus: Consultancy; Rigel: Consultancy; ADC Therapeutics: Consultancy. Ulrickson: Miltenyi Biomedicine: Honoraria; ADC Therapeutics.: Consultancy; Bristol Myers Squibb: Consultancy; Stemline: Consultancy; Autolus: Consultancy. Reshef: Abbvie: Research Funding; TScan: Consultancy, Research Funding; TCR2: Research Funding; Sana Biotechnology: Consultancy; Immatics: Research Funding; Autolus: Consultancy; Synthekine: Research Funding; J&J: Research Funding; Genentech: Research Funding; Precision Biosciences: Research Funding; Sanofi: Research Funding; Atara Biotherapeutics: Research Funding; Bayer: Consultancy; Gilead Sciences: Consultancy, Research Funding; Quell Biotherapeutics: Consultancy; CareDx: Research Funding; Cabaletta: Research Funding; BMS: Research Funding; Takeda: Research Funding; Orca Bio: Consultancy; Incyte: Consultancy, Research Funding; Allogene: Consultancy. Cassaday: Pfizer: Consultancy, Honoraria, Research Funding; PeproMene Bio: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Honoraria, Research Funding; Jazz: Consultancy; Incyte: Research Funding; Autolus: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Research Funding; Seagen: Ended employment in the past 24 months; Servier: Consultancy, Research Funding; Vanda Pharmaceuticals: Research Funding. Hill: Kite/Gilead: Speakers Bureau; March Biosciences: Consultancy. Lee: ScientiaCME: Consultancy; Sanofi: Consultancy, Honoraria, Speakers Bureau; Aptitude Health: Consultancy; SEI: Consultancy; Incyte: Consultancy, Honoraria, Research Funding. Kota: Novartis: Honoraria; Pfizer: Honoraria; Kite Pharma: Honoraria. Sasine: Kite Pharma: Consultancy; Genmab: Consultancy; Autolus: Consultancy. Merchant: Innate Pharma: Research Funding; Abbvie: Consultancy, Speakers Bureau; Oncovalent: Consultancy, Research Funding; Amgen: Consultancy; Genmab: Consultancy, Speakers Bureau; IMMpact Bio: Research Funding; BMS: Speakers Bureau. Pullarkat: Amgen: Speakers Bureau; Jazz: Speakers Bureau; Sobi: Speakers Bureau; Alexion: Honoraria; Rigel: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Speakers Bureau; sanofi: Consultancy. Hilal: BeiGene: Consultancy, Research Funding. Faramand: Autolus: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria; Orca Bio: Research Funding; Novartis: Research Funding; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees. Solh: GlaxoSmithKline: Speakers Bureau; Bristol Myers Squibb: Consultancy, Speakers Bureau; Sanofi: Consultancy. Majhail: Caribou Biosciences: Research Funding; Anthem: Consultancy. Hoeg: Orca Bio: Research Funding. Oliai: Orca Bio: Research Funding; Pfizer: Research Funding; Arog: Research Funding; Ascentage: Research Funding; Jazz Pharmaceuticals: Research Funding; Amgen: Research Funding; Roche: Research Funding; University of California, LA: Current Employment. Koura: BMS: Other: ad board. Bachanova: Gamida Cell: Research Funding; Incyte: Research Funding; Citius: Research Funding; CRISPR: Consultancy; Astra Zeneca: Consultancy; Allogene: Consultancy; Miltenyi: Other: DSMB. Oluwole: Gilead Sciences: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Nektar: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy; AbbVie: Consultancy; Caribou Biosciences: Consultancy; Bioheng: Consultancy; Allogene: Research Funding; Daichi Sankyo: Research Funding; TGR: Consultancy; Cargo: Consultancy; ADC: Consultancy, Speakers Bureau; Epizyme: Consultancy. Shaughnessy: Autolus, Sanofi: Consultancy; BMS: Speakers Bureau; Sanofi: Speakers Bureau. Shah: Jazz Pharmaceuticals: Consultancy; Autolus, Beigene, Century Therapeutics, Deciphera, Jazz, Kite/Gilead, Pfizer, Precision Biosciences, Novartis, Takeda: Consultancy; Pepromene Bio: Other: DSMB; Kite Pharma: Consultancy; Eli Lilly: Consultancy; Bristol Myers Squibb: Consultancy; AstraZeneca: Consultancy; Amgen: Consultancy; Jazz Pharmaceuticals, Kite-Gilead, Servier: Research Funding; Adaptive Biotechnologies: Consultancy. Muffly: Bristol Myers Squibb: Consultancy; Jasper: Research Funding; Vor: Consultancy, Research Funding; Autolus: Consultancy; Pfizer: Consultancy; Wugen: Research Funding; Adaptive: Research Funding; Cargo Therapeutics: Consultancy; Astellas: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. Park: Curocell: Current equity holder in publicly-traded company; Takeda: Consultancy; Autolus, Fate Therapeutics, Genentech, InCyte, Servier, Sobi, Takeda (Institution): Research Funding; Adaptive Biotechnologies, Affyimmune, Allogene, Amgen, Artiva Biotherapeutics, Autolus, Bright Pharmaceutical Services, BMS, Caribou Biosciences, Curocell, Galapagos, Gilead Sciences, Intellia, In8Bio, Kite, Novartis, Pfizer, Servier, Sobi, Synthekine: Consultancy.

*signifies non-member of ASH