Multinational Retrospective Analysis of Bridging Therapy Prior to Chimeric Antigen Receptor T Cells for Relapsed/Refractory Acute Lymphoblastic Leukemia in Children and Young Adults

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.2135-2135
• Main Authors: Breidenbach, Maike, Bader, Peter, Attarbaschi, Andishe, Rossig, Claudia, Meisel, Roland, Metzler, Markus, Subklewe, Marion, Mueller, Fabian, Schlegel, Paul-Gerhardt, Teichert von Lüttichau, Irene, Bourquin, Jean-Pierre, Escherich, Gabriele, Cario, Gunnar, Lang, Peter, Krauss, Ramona, von Stackelberg, Arend, Willier, Semjon, Peters, Christina, Feuchtinger, Tobias
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-190117

Background: Chimeric antigen receptor (CAR) T cells targeting CD19 are a well-established treatment option for children and young adults suffering from relapsed and/or refractory B-lineage acute lymphoblastic leukemia. Nonetheless, there is still insufficient data about the proper management of bridging therapy between eligibility for therapy and administration of CAR T cells taking into consideration that most of the patients are heavily pretreated. Bridging therapy has been designed to achieve a low leukemia burden prior to CAR T cell infusion. However, systematic data of bridging therapy are still limited and the effect of bridging therapy on outcome, side effects and response to CAR T cell therapy is still poorly understood. With this retrospective, multinational, large-scale study, we strive to understand the impact of low- and high-intensity bridging regimens on a variety of outcome parameters in order to improve the basis for clinical decision making in bridging therapy prior to CAR T cell administration. Methods: Real-world data were collected from 83 patients receiving 88 CAR T cell therapies from twelve different sites in Germany, Austria and Switzerland. Data were collected anonymously via paper case report forms and subsequently analyzed. Performed treatments were classified into the categories 1) no systemic therapy, 2) low-intensity therapy and 3) high-intensity therapy. Bridging therapies were defined as high-intensity if at least one chemotherapeutic agent of the following was given: cyclophosphamide/ifosfamide, etoposide, anthracyclines or other agents with high toxicity potential (intravenous methotrexate, platinum-based antineoplastic drugs, thiotepa, high-dose cytarabine, fludarabine). Low-intensity bridging therapies comprised the administration of steroids, vincristine, low-dose cytarabine, PEG-asparaginase/Erwinia asparaginase and oral maintenance therapy (mercaptopurine, thioguanine, oral methotrexate, hydroxyurea). The administration of specific chemotherapeutic agents as well as immunotherapies and targeted therapies was assessed. CAR therapies comprised CD19 2 nd generation CAR T cell products from commercial and academic providers. We then analyzed the impact of different bridging regimens on several outcome parameters such as overall and disease-free survival, adverse events, tumor burden and performance status at defined time points (eligibility, leukapheresis if performed, lymphodepletion/CAR T cell infusion). Results: 33 of