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3498 Efficacy and Tolerance of Brexucabtagene Autoleucel in Adults with Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia : A Graall Study from the Descar-T Registry

Program: Oral and Poster Abstracts
Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, Lymphoid Leukemias, ALL, Biological therapies, adult, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, real-world evidence, Therapies, Lymphoid Malignancies, Adverse Events, Study Population, Human
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Florence Rabian, MD1,2*, David Beauvais, MD3*, Tony Marchand, MD4,5,6*, Sabine Furst, MD7*, Anne Huynh, MD8*, Eolia Brissot9*, Sebastien Maury10*, Ludovic Gabellier, MD, PhD11*, Patrice Chevallier, MD12, Michael Loschi, MD, PhD13*, Stéphanie Nguyen Quoc, MD, PhD14*, Marie Balsat, MD15*, Ingrid Lafon, MD16*, Amandine Fayard, MD17*, Vincent Camus, MD18*, Célestine Simand, MD, PhD19*, Niels Moya, MD20*, Cristina Castilla-Llorente, MD21*, Magalie Joris, MD22*, Ana Berceanu, MD23*, Anne Thiebaut, MD24*, Véronique Lhéritier25*, Eve Gehlkopf, MD26*, Gabrielle Roth-Guepin, MD27*, Thibaut Leguay, MD28* and Nicolas Boissel, MD, PhD29,30*

1Hematology Adolescents and Young Adult Unit, Saint-Louis Hospital, APHP, Paris, France, Paris, France
2URP-3518, Institut de Recherche Saint-Louis, Université de Paris Cité, Paris, France
3CHU Lille, Infinite U1286, INSERM, Lille, FRA
4Hematology Department, CHU Rennes, Rennes, France
5Université Rennes 1, Rennes, France
6Institut National de la Santé et de la Recherche Médicale (INSERM) U1236, Rennes, France
7Institut Paoli-Calmettes, Marseille, FRA
8Institut Universitaire du Cancer Toulouse - Oncopole, Toulouse, France
9Hôpital Saint-Antoine, Sorbonne University, INSERM UMRs 938, Paris, France
10Hematology Department, Hôpitaux universitaires Henri Mondor AP-HP & Université Paris Est Créteil, Créteil, France
11Clinical Hematology Department, Montpellier University Hospital, MONTPELLIER, France
12Service d'hématologie, CHU de Nantes, Nantes, France
13Hematology Department, Nice University Hospital, Cote d’Azur University, Nice, France
14Hematology Department, Sorbonne Université, Hôpital Pitié-Salpêtrière, APHP, Paris, France
15Clinical Hematology Department, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France, Lyon, France
16Service d'Hematologie, Institut de Cancérologie de Bourgogne (ICB), Polyclinique du Parc Drevon (Dijon), Dijon, France
17hématologie clinique et thérapie cellulaire, CHU Estaing, Clermont-Ferrand, FRA
18Department of Hematology, Centre Henri Becquerel, Rouen, France
19ICANS, Hematology Department, CHU Strasbourg, Illkirch, France
20CHU Poitiers, Poitiers, France
21Department of Hematology, Gustave Roussy Cancer Campus, Villejuif, France
22Service d’Hématologie Clinique, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, FRA
23Department of Clinical Hematology, CHU de Besançon, Besançon, France
24service d'hématologie clinique, CHUGA Grenoble, Grenoble, France
25Service d’Hématologie Coordination GRAALL, HCL, Hôpital Lyon Sud, Pierre Bénite, France
26Medical and Scientific Department, LYSARC, Hôpital Lyon-Sud, Pierre-Bénite, France
27Department of clinical hematology, CHRU NANCY, Vandoeuvre Les Nancy, France
28Hematology, CHU Bordeaux, Hôpital du Haut-Lévêque, Pessac, France
29Hôpital Saint-Louis, Paris, France
30Institut Universitaire d'Hématologie, EA-3518, University Hospital Saint-Louis, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France

Background : Brexucabtagene autoleucel (brexu-cel) was recently approved for adult patients with relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) based on the results of the ZUMA-3 phase 2 study. After a median follow-up of 39 months, brexu-cel showed a complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate of 71% and a median overall survival of 26 months (Shah B, et al. ASCO 2023). In the present study, we aimed at investigating the efficacy and safety of brexu-cel in a real-life cohort of adult BCP-ALL patients included in the French early access program.

Methods : In this Group for Research on Adult Acute Lymphoblastic leukemia (GRAALL) study, we performed an analysis of the DESCAR-T registry which collects real-life data of patients treated with CAR T-cells since July 2018 in France. All patients who underwent a leukapheresis with an intent to manufacture brexu-cel were included (N=80). Efficacy and safety analyses were performed in the 64/66 infused patients with available response assessment after infusion. The data cut-off was June 2023. The present study reports on best overall response, overall survival (OS), relapse-free survival (RFS), as well as immune effector cell-associated neurotoxicity syndrome (ICANS), and cytokine release syndrome (CRS) incidence and grading (according to ASTCT Consensus).

Results : Between May 2019 and February 2023, 80 adults with R/R BCP-ALL from 22 French centers had a leukapheresis for brexu-cel. Among them, 14 patients (18%) were not infused because of death (8 pts), progression (1 pt), manufacturing failure (2 pts), or other causes (3 pts). Among the 64 infused patients with available response assessment, median age was 43.5 yrs (range, 22-69). A Philadelphia(Ph)-chromosome was found in 20/64 (31%). Patients had received a median of 3 (range, 1-6) prior lines of treatment including blinatumomab, inotuzumab ozogamicin and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 67%, 19% and 70% of patients respectively. Twelve patients (19%) had an active CNS disease (CNS2/3) prior to apheresis and 18/40 (45%) had bone marrow blasts ≥ 25% before lymphodepletion (LD). ECOG before infusion was ≥2 in 6/64 (9%) patients. All patients received fludarabine and cyclophosphamide as LD. Median time from apheresis to infusion was 40 days (range, 27-99). CRS and ICANS occurred in 48/64 (77%, grade 3+ in 6%) and 28/64 (45%, grade 3+ in 8%) of patients respectively and were reversible. A CR was achieved in 49/64 patients (77%) of whom 23/25 (92%) were MRD-negative. An older age, a prior allo-HSCT, and the occurrence of CRS were associated with significantly higher CR rates. The median follow-up was 13 months. Three patients were bridged to an allo-HSCT in continuous complete remission (second allo-HSCT for 2 of them). The median RFS and OS were 12.9 months and 15.6 months respectively (Figure). In patients who achieved a CR, median OS was 25.8 months (Figure). Patients with CNS involvement before leukapheresis had a significantly shorter RFS (HR 5.4, 95%CI 1.9-15.8, p=0.002) and OS (HR 3.3, 95%CI 1.4-8.2, p=0.008). Number of prior treatment lines, prior inotuzumab, prior blinatumomab, or pre-LD BM blast% were not associated with outcome. A better OS was observed in patients with prior allo-HSCT (HR .4, 95%CI 0.2-0.9, p=0.04).

Conclusion : This multicenter real-life study confirms the efficacy and acceptable safety profile of brexu-cel in adult patients with R/R BCP-ALL. It also suggests that patients with CNS involvement, that were not eligible to ZUMA-3 study, have a limited benefit of brexu-cel when compared to other patients.

Disclosures: Rabian: Kite-Gilead: Honoraria; Jazz Pharmaceuticals: Honoraria. Beauvais: Kite/Gilead: Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board. Marchand: Astellas: Consultancy; Sobi: Consultancy; Jazz Pharmaceuticals: Consultancy, Other: travel fees; Servier: Consultancy, Other: Travel fees. Huynh: Medac: Other: Advisory board; Servier: Other: Advisory board; Astellas: Other: Advisory board; Pfizer: Other: advisory board; Neovii: Other: Advisory board; Jazz: Other: travel fees, advisory board; Novartis: Other: travel fees, advisory board. Chevallier: Incyte: Honoraria, Research Funding; Sanofi: Honoraria; Mallinckrodt Pharmaceuticals: Honoraria; Takeda: Honoraria; Immedica Pharma: Honoraria; Servier: Honoraria. Loschi: Sanofi: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; MSD: Honoraria; Medac: Honoraria; Kartos: Honoraria; Jazz: Honoraria; Sobi: Honoraria; GSK: Honoraria; Telios: Honoraria; Gilead: Honoraria; BMS: Honoraria; AstraZeneca: Honoraria; Alexion: Honoraria. Camus: Kite-Gilead: Honoraria. Castilla-Llorente: Gilead/Kite: Consultancy, Other: Travel support; Nektar Therapeutics: Consultancy. Boissel: Novartis: Consultancy, Honoraria, Other: Advisory role, Research Funding; Servier: Consultancy, Honoraria, Other: Advisory role; ARIAD/Incyte: Honoraria; Astellas Pharma: Honoraria; Amgen: Consultancy, Honoraria, Other: Expert Testimony and advisory role, Research Funding.

*signifies non-member of ASH