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2333 Real-World Outcomes of CD19-Targeted CAR T-Cell Therapy in Adult and Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia (B-ALL): Insights from the GoCART Coalition on Behalf of the PDWP, ALWP, and CTIWP of the EBMT

Program: Oral and Poster Abstracts
Session: 906. Outcomes Research: Lymphoid Malignancies Excluding Plasma Cell Disorders: Poster I
Hematology Disease Topics & Pathways:
Adult, Clinical Practice (Health Services and Quality), Pediatric, Adverse Events, Young adult , Study Population, Human
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Valentin Ortiz-Maldonado, MD, PhD, MSc1,2,3,4, Jacques-Emmanuel Galimard, PhD5*, Giorgio Ottaviano6*, Anna Alonso-Saladrigues, MD1,7*, Shatha Y. Farhan, MD8, Sowjanya Vuyyala, MBBS9, Eva Michel10*, Fizza Imran10*, Nazaret Sánchez-Sierra, MD11*, Nuria Martínez-Cibrián, MD12*, Samppa Ryhänen Sr., MD, PhD13,14, Richard Mitchell, MBBS15*, Stephan Mielke, MD16, Soeren Lykke Petersen, MD, MSc17*, Anne Sirvent18*, Thomas Pabst19, Jurgen Kuball, MD20, Pere Barba, MD21, Antonio Perez, MD, PhD22*, Andishe Attarbaschi, MD23,24*, Arnon Nagler, MD, MSc25,26*, Jose Antonio Pérez-Simón, MD, PhD27, Malte von Bonin, MD28*, Emma Nicholson, MD29*, David Beauvais, MD30*, Julio Delgado, MD, PhD1,3,31*, Susana Rives32*, Krzysztof Kalwak, MD, PhD33*, Fabio Ciceri, MD34*, Annalisa Ruggeri, MD, PhD35*, Adriana Balduzzi, MD6 and Sebastian Giebel, MD, PhD36*

1University of Barcelona, Barcelona, Spain
2Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
3Hospital Clínic de Barcelona, Barcelona, Spain
4Hematology Department, Hospital Clínic Barcelona, Barcelona, Spain, Seattle, WA
5European Society for Blood and Marrow Transplantation, Paris, France
6Department of Pediatrics, Bone Marrow Transplant Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
7Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Spain
8Department of Stem Cell Transplant and Cellular Therapy, Henry Ford Hospital, Detroit, MI
9Hematology and Oncology, Mayo Clinic, Rochester, MN
10EBMT Paris Study Unit, Saint Antoine Hospital, INSERM UMR-S 938, Sorbonne University, Paris, France
11Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu de Barcelona, Barcelona, Spain
12Hematology Department, Hospital Clínic Barcelona, Barcelona, Spain, Barcelona, Spain
13Children’s Hospital, University of Helsinki, Helsinki, Finland
14Pediatric Research Center, Helsinki University Hospital, Helsinki, Finland
15Kids Cancer Centre, Sydney Children`s Hospital, Sydney, Australia
16Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska Comprehensive Cancer Center and ATMP Center, Karolinska Institutet and University Hospital, Stockholm, Sweden
17Department of Hematology, Copenhagen University Hospital, Copenhagen, Denmark
18Pediatric BMT Unit, Montpellier, France
19Department of Medical Oncology, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland
20Department of Hematology, University Medical Centre, Utrecht, Netherlands
21Department of Hematology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
22Pediatric Hemato-Oncology Department, Hospital Universitario La Paz, Madrid, Spain
23Department of Pediatric Hematology and Oncology, St. Anna Kinderspital, Vienna, Austria
24St. Anna Children´s Cancer Research Institute (CCRI), Vienna, Austria
25Chaim Sheba Medical Center, Tel-Hashomer, Israel
26Tel Aviv University, Tel-Hashomer, Israel
27Department of Hematology, University Hospital Virgen del Rocío, Sevilla, Spain
28University Hospital TU Dresden, Dresden, Germany
29Royal Marsden NHS Foundation Trust, London, United Kingdom
30Hematology Department, CHU Lille, Lille, France
31Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain
32Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, Esplugues De Llobregat, Barcelona, AL, Spain
33Department of Pediatric Hematology, Oncology and BMT, Wroclaw Medical University, Wroclaw, Poland
34Ospedale San Raffaele, Milan, Italy
35Hematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
36Department of Hematology and Bone Marrow Transplantation, Maria Sklodowska-Curie Institute of Oncology, Gliwice, Poland

Background: In 2015 the first B-cell acute lymphoblastic leukemia (B-ALL) patient receiving CAR T-cell therapy in Europe was reported to the EBMT registry. Today, the EBMT registry counts with more than 9000 patients treated with CAR T-cell therapies across all indications. Here, on behalf of the GoCART coalition, we present the outcomes of the largest European cohort of B-ALL patients treated with autologous, second generation, CD19-targeted CAR T-cells to date.

Methods: Adult and paediatric patients with B-ALL received treatment with CAR T-cell therapy using either academic or commercially available products in 40 centres across 17 different countries. Safety was retrospectively assessed as per ASCTC 2019 consensus grading and CTCAE, and efficacy as per NCCN guidelines. Relapse incidence was defined as haematological relapse or progression after CART with non-relapse mortality as competing event. Leukemia free survival (LFS) was defined as being alive without occurrence of relapse. Follow-up includes patients treated from 2016 to Dec 2023 until data cutoff in June 2024.

Results: A total of 345 patients (173 adults and 172 pediatrics) received therapy from 2016 to 2023 with tisagenlecleucel (65.2%), varnimcabtagene autoleucel (25.8%), brexucabtagene autoleucel (5.5%), and others (3.5%). Median age at infusion was 18 yrs. (range, 1.1-78.2) and 41.7% were females. High-risk features were identified including cytogenetic/genomic high-risk as per ELN guidelines (33.8%), relapse after allo-HCT (57.7%), early relapse (<1 year) after prior allo-HCT (30.4%), ≥3 prior treatment lines (55.5%) including prior exposure (and refractoriness) to blinatumomab and inotuzumab in 27.3% (34%) and 28.8% (32.3%), respectively. Median time from diagnosis to CART infusion was 2.8 years (0.1-17.9). Median time from last relapse prior CART to infusion was 2 months (range, 0.9-38.4). Bridging therapy was administered in 86.4% (298) of patients based on high or low intensity chemotherapy (32.1% or 26.5%, respectively), inotuzumab-ozogamicin (13.4%), TKI (8.2%), involved-site therapy (intrathecal chemotherapy, radiotherapy, orchiectomy) (3.5%), and blinatumomab (2.6%), alone or in combination. Prior to infusion, 34.7% had more than 5% BM blast count, 16.3% had circulating blasts in PB, and 20.6% had extramedullary disease. Lymphodepletion was performed in all but one patient, based on fludarabine and cyclophosphamide regimens. The reverse Kaplan-Meier median follow-up was of 2.2 years. The incidence of any grade (and severe) CRS was 71.6% (14.5%), and for ICANS was 15.7% (7.6%). The cumulative incidence of MRD-negative CR at month +3 was 76.9% (71.9-81.1), followed by a 2-year overall survival of 64.6% (58.7-69.8), leukemia-free survival of 48% (42.1-53.7), and relapse incidence of 45.5% (39.6-51.2). Non-relapse mortality at 2 years was 6.5% (4-9.6), 2-year cumulative incidence of subsequent HSCT of 33.3% (28-38.7) and second CAR-T infusions of 12.4% (8.8-16.6). Allogeneic HSCT after CAR-T was performed in 113 cases including 67 (59.3%) HSCT-naïve patients, due to molecular or overt disease relapse (60.9%), and other non-relapse reasons including suboptimal CAR-T persistence/B-cell aplasia (19.1%), pre-CAR-T high-risk features (13.6%), second malignancies (1.8%), and others. Second CAR-T infusions were performed in 39 cases due to molecular or overt disease relapse (79.5%) or suboptimal CAR-T persistence/B-cell aplasia in the absence of relapse (20.5%).

Conclusions: The results from this European study demonstrate that CD19-targeted CAR T-cell therapy is an effective treatment for patients with high-risk B-cell ALL, providing substantial leukemia-free survival and overall survival rates despite the high-risk nature of the patient population. The necessity for bridging therapies and subsequent consolidative approaches, such as HSCT and second CAR T infusions, underscores the complexity and tailored nature of managing R/R B-ALL. These findings support the continued use and further investigation of CAR T-cell therapy in diverse clinical settings, emphasizing the importance of post-infusion strategies to sustain long-term remission. This will provide deeper insights into the factors influencing outcomes and help refine treatment protocols to improve patient care.

Disclosures: Ortiz-Maldonado: Pfizer: Honoraria; Miltenyi: Honoraria; Kite/Gilead: Honoraria, Other: Travel grants; Janssen: Honoraria, Other: Travel grants; Celgene-BMS: Honoraria, Other: Travel grants; Hospital Clínic de Barcelona: Current Employment; Novartis: Honoraria. Martínez-Cibrián: Kite/Gilead: Honoraria, Other: Travel Expenses. Ryhänen: Medac: Other: Travel grants; Jazz Pharmaceuticals: Other: Travel grants; Amgen: Consultancy. Mielke: Kiadis Pharma: Research Funding; Celgene/BMS: Speakers Bureau; Immunicum/Mendes: Membership on an entity's Board of Directors or advisory committees; Janssen: Speakers Bureau; KITE/GILEAD: Research Funding, Speakers Bureau; Miltenyi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Speakers Bureau; Scientify Research: Current equity holder in private company; SWECARNET: Membership on an entity's Board of Directors or advisory committees. Petersen: Novartis, Kite/Gilead: Speakers Bureau. Kuball: Gadeta: Current holder of stock options in a privately-held company; Gadeta: Consultancy, Research Funding; Miltenyi Biotech: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Barba: Autolus: Consultancy; Kite-Gielead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Honoraria; Incyte: Honoraria; BMS: Honoraria. Pérez-Simón: Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; J&J: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. von Bonin: Kite/Gilead: Other: Travel grants; Novartis: Other: Travel grants; BMS: Other: Travel grants; Janssen: Other: Travel grants. Nicholson: BMS/Celgene: Honoraria; Novartis: Honoraria; Kite/Gilead: Honoraria, Research Funding; Autolus: Membership on an entity's Board of Directors or advisory committees. Beauvais: Kite/Gilead: Consultancy, Honoraria. Rives: Amgen: Honoraria; Clinigen: Honoraria; Pfizer: Honoraria; Kite/ Gilead: Honoraria; Celgene/ Bristol Myers Squibb: Honoraria; Servier: Honoraria; Novartis: Honoraria, Other: DMSB in trial sponsored by Novartis; Autolus: Other: Data monitoring committee. Kalwak: Merck: Speakers Bureau; Pierre Fabre: Other: Travel Grant, Speakers Bureau; Novartis: Speakers Bureau; Medac: Speakers Bureau. Balduzzi: Neovii: Speakers Bureau; Medac: Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau. Giebel: Miltenyi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS, Janssen, Pfizer: Speakers Bureau; Immunicum/Mendes: Membership on an entity's Board of Directors or advisory committees; Equity Ownership (Private company): Research Funding; Gilead/Kite: Research Funding, Speakers Bureau; Kiadis Pharma, The Netherlands: Research Funding.

OffLabel Disclosure: This study includes the outcomes of several autologous, second generation, CD19-targeter CAR T-cell products used in the "real world" setting, either commercially available or academic/investigational producst without a label.

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