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4877 The Impact of Inotuzumab Ozogamicin (InO) Treatment on Brexucabtagene Autoleucel (Brexu-cel) Outcomes in Adults with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (B-ALL)

Program: Oral and Poster Abstracts
Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster III
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Biological therapies, Antibody Therapy, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Therapies, Immunotherapy, Lymphoid Malignancies
Monday, December 11, 2023, 6:00 PM-8:00 PM

Ibrahim Aldoss, MD1, Gregory W Roloff, MD2, Anjali S. Advani, MD3, Noam E. Kopmar, MD4, Chenyu Lin, MD5, Simone E. Dekker, MD, PhD6, Vishal K Gupta, MD7, Nikeshan Jeyakumar, MD8*, Timothy E O'Connor, MD9, Amy Zhang, PhD10*, Katharine Miller, PhD, MPH10*, Kaitlyn C Dykes, MD11*, Mohamed Ahmed12, Hector Zambrano13*, Danielle Bradshaw, MD14*, Santiago Mercadal, MD15*, Marc Schwartz, MD16*, Sean Tracy, MD, PhD17, Bhagirathbhai Dholaria, MBBS18, Michal Kubiak, MD14, Akash Mukherjee, MD19*, Navneet Majhail, MD, MS, FASTCT20, Minoo Battiwalla, MD21, Luke Mountjoy, DO22, Shahbaz A. Malik, MD23, John Mathews, MD24*, Paul Shaughnessy, MD25, Aaron C. Logan, MD, PhD26, Abdullah Ladha, MD27*, George Yaghmour, MD28, Maryann Stefan3*, Caitlin Guzowski, MBA29*, Rasmus T. Hoeg, MD30*, Talal Hilal, MD31, Jozal Moore, MD32, Kristen M. O'Dwyer, MD32, Stephanie B. Tsai, MD, MS9, Joshua Sasine, MD12, Melhem M. Solh, MD29, Catherine J. Lee, MD33, Vamsi K. Kota, MD34, Divya Koura, MD11, Muthu Veeraputhiran, MD19*, Betsy Blunk13*, Jessica T. Leonard, MD35, Caspian H. Oliai, MD7, Veronika Bachanova, MD, PhD17, Wendy Stock, MD2, Ahmed Galal, MD5, Vinod Pullarkat, MD36, Ryan D Cassaday, MD4, Bijal D. Shah, MD37, Rawan Faramand, MD38 and Lori S. Muffly, MD8

1City of Hope, Duarte, CA
2University of Chicago, Chicago, IL
3Cleveland Clinic Foundation, Cleveland, OH
4University of Washington, Seattle, WA
5Duke University School of Medicine, Durham, NC
6Department of Hematology & Medical Oncology, Oregon Health & Science University, Portland, OR
7University of California Los Angeles, Los Angeles, CA
8Division of Blood and Marrow Transplantation & Cellular Therapy, Stanford University School of Medicine, Palo Alto, CA
9Loyola University, Maywood, IL
10Stanford University School of Medicine, Stanford, CA
11University of California San Diego, La Jolla, CA
12Cedars-Sinai Medical Center, Los Angeles, CA
13Sarah Cannon Research Institute, Nashville, TN
14Augusta University, Augusta, GA
15University of Utah, Salt Lake City, UT
16Division of Hematology, University of Colorado, Aurora, CO
17University of Minnesota, Minneapolis, MN
18Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN
19University of Arkansas for Medical Sciences, Little Rock, AR
20Sarah Cannon Transplant and Cellular Therapy Network, Nashville, TN
21Sarah Cannon Transplant and Cellular Therapy Program at TriStar Centennial Medical Center, Nashville, TN
22Colorado Blood Cancer Institute and Sarah Cannon Cancer Institute at Presbyterian/St Luke’s Medical Center, Denver, CO
23St. David's South Austin Medical Center, Austin, TX
24Sarah Cannon and Texas Oncology Transplant and Cellular Therapy Program at Medical City Dallas, Dallas, TX
25Sarah Cannon Transplant and Cellular Therapy Program at Methodist Hospital, San Antonio, TX
26Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA
27University of Southern California, Los Angeles, CA
28Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA
29Northside Hospital, Atlanta, GA
30Department of Internal Medicine, Division of Cellular Therapy, Bone Marrow Transplantation and Malignant Hematology, University of California Davis, Sacramento, CA
31Mayo Clinic, Phoenix, AZ
32University of Rochester, Rochester, NY
33Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA
34Georgia Cancer Center, Augusta University, Augusta, GA
35Oregon Health & Science University, Portland, OR
36Hematology/HCT, City of Hope National Medical Center, Duarte, CA
37Moffitt Cancer Center and Research Institute, Tampa, FL
38Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL

  1. Cellular Immunotherapies: Late Phase and Commercially Available Therapies

The Impact of Inotuzumab Ozogamicin (InO) Treatment on Brexucabtagene Autoleucel (Brexu-cel) Outcomes in Adults with Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia (B-ALL)

Introduction: Brexu-cel is the first approved CD19-directed chimeric antigen receptor (CAR) T-cell therapy for adult patients (pts) with relapsed/refractory (r/r) B-ALL. InO, an anti-CD22 antibody drug conjugate, is also approved for the same indication. With the accessibility to several targeted therapies in r/r B-ALL, the optimal sequence remains uncertain. The effect of prior treatment with InO on brexu-cel outcomes remains underreported, especially as a bridging therapy, as well as the effect of previous response to InO on post brexu-cel outcomes.

Methods: This is a retrospective multicenter analysis from 25 U.S. institutions of adults (≥18 years) with r/r B-ALL treated with commercial brexu-cel from 2021 to 2023 post FDA approval. Methodologies for assessing minimal residual disease (MRD) (minimal threshold of 10-4) included flow cytometry, NGS, or qPCR depending on institutional practice. Progression-free survival (PFS) and overall survival (OS) were calculated from day of brexu-cel infusion and were not censored for hematopoietic cell transplant (HCT) or maintenance. All living patients were censored at the time of last follow-up prior to data lock, which occurred on June 30, 2023.

Results: Among 152 infused, 83 (54.6%) had pre-CAR InO therapy (InO-exposed), with a median of 3 administered doses (range: 1-22). Within the InO-exposed cohort, 23 (28%) pts received InO as a CAR T-cell bridging therapy (ie, between apheresis and lymphodepletion) with or without pre-apheresis and 60 (72%) pts received InO only during pre-apheresis. Baseline characteristics for InO exposed and InO-naïve pts are shown in Table 1. InO-exposed pts had higher median prior lines of therapies (4 vs. 3; p= 0.05), more frequently had active disease (≥5% marrow blasts) at the time of apheresis (67% vs. 44%, p= 0.02), and had lower incidence of Ph+ disease (19% vs. 45%, p=0.003), compared to InO-naïve pts, respectively.

The incidences of cytokine release syndrome (CRS) (85% vs. 85%, p= 0.26) and ICANS (58% vs. 57%, p= 0.36) post infusion were similar, and post-infusion death in remission occurred in 17% and 12% among InO-exposed and InO-naïve pts, respectively. Morphological complete remission (CR) and MRD- rates following brexu-cel infusion were 89% and 77% for InO-exposed pts, and 92% and 70% for InO-naive pts, respectively. Post CAR therapy, more InO-naïve pts underwent consolidation/maintenance therapy (transplant, chemotherapy, or TKIs) compared to InO-exposed pts (41% vs. 19%, p= 0.004).

The median follow-up after brexu-cel was 8.4 (range) months. Median OS (not reached (NR) vs. 12 months; p= 0.033) and median PFS (NR vs. 7 months; p= 0.029) were superior in InO-naïve pts compared to InO-exposed pts, respectively. However, after adjusting for pre-apheresis disease burden and post-CAR maintenance therapy, there were no longer significant differences in OS (HR= 1.25;95%CI: 0.62-2.53; p= 0.53) or PFS (HR= 1.24;95%CI:0.71-2.16, p=0.45) based on pre-CAR InO exposure. When InO-exposed pts were stratified based on prior InO-response (CR vs. no response), InO-responsive pts had superior estimated 12-month OS (64%) and PFS (38%) relative to InO-refractory pts (OS: 33%; PFS: 34%), but inferior to InO-naïve pts (OS: 75%; PFS 56%), with p-values of 0.0001 and 0.021 for OS and PFS, respectively (Figure 1). The timing of pre-CAR InO therapy did not impact brexu-cel survival outcomes, with comparable estimated 12-month OS (43% vs. 58%, p= 0.35) and PFS (46% vs. 38%, p= 0.57) for InO-exposed pts during bridging therapy and patients who received InO as a therapy prior to apheresis.

Conclusion: After adjusting for pre-CAR disease burden and post-CAR consolidation/maintenance, we found that prior InO exposure does not significantly associate with PFS or OS following brexu-cel. However, relative to InO-responsive patients, patients who were InO-refractory appear to have worse post-CAR survival outcomes. Finally, timing of InO administration (ie as a prior line of therapy or as CAR bridging) did not influence outcomes brexu-cel outcomes.

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

*signifies non-member of ASH