https://phaidra.vetmeduni.ac.at/o:3428 Patient-derived xenograft models of ALK+ ALCL reveal preclinical promise for therapy with brigatinib Prokoph, Nina Nina Prokoph University of Cambridge Turner, Suzanne D. Suzanne D. Turner 0000-0002-8439-450 University of Cambridge / Masaryk University Brugières, Laurence Laurence Brugières Institut Gustave Roussy Riguad, Charlotte Charlotte Riguad Institut Gustave Roussy Murray, Matthew J. Matthew J. Murray 0000-0002-4480-1147 University of Cambridge / Cambridge University Hospitals NHS Foundation Trust Johnston, Robert Robert Johnston Royal Belfast Hospital for Sick Children Geoerger, Birgit Birgit Geoerger Université Paris-Saclay / Institut Gustave Roussy Kenner, Lukas Lukas Kenner 0000-0003-2184-1338 University of Veterinary Medicine Vienna / Medical University of Vienna Merkel, Olaf Olaf Merkel Medical University of Vienna Fend, Falko Falko Fend University of Tübingen Burke, G. A. Amos G. A. Amos Burke 0000-0003-2671-9972 Cambridge University Hospitals NHS Foundation Trust Montes-Mojarro, Ivonne A. Ivonne A. Montes-Mojarro University of Tübingen Matthews, Jamie D. Jamie D. Matthews University of Cambridge Trigg, Ricky M. Ricky M. Trigg University of Cambridge Wiley text eng Anaplastic large-cell lymphoma (ALCL) is a T-cell malignancy predominantly driven by the oncogenic anaplastic lymphoma kinase (ALK), accounting for approximately 15% of all paediatric non-Hodgkin lymphoma. Patients with central nervous system (CNS) relapse are particularly difficult to treat with a 3-year overall survival of 49% and a median survival of 23.5 months. The second-generation ALK inhibitor brigatinib shows superior penetration of the blood-brain barrier unlike the first-generation drug crizotinib and has shown promising results in ALK+ non-small-cell lung cancer. However, the benefits of brigatinib in treating aggressive paediatric ALK+ ALCL are largely unknown. We established a patient-derived xenograft (PDX) resource from ALK+ ALCL patients at or before CNS relapse serving as models to facilitate the development of future therapies. We show in vivo that brigatinib is effective in inducing the remission of PDX models of crizotinib-resistant (ALK C1156Y, TP53 loss) ALCL and furthermore that it is superior to crizotinib as a second-line approach to the treatment of a standard chemotherapy relapsed/refractory ALCL PDX pointing to brigatinib as a future therapeutic option. Large-Cell Lymphoma; Lung-Cancer; Solid Tumors; Open-Label; Crizotinib; Mutations; Resistance; Alectinib; Children; Stat3 http://creativecommons.org/licenses/by/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:3428/download 10.1111/bjh.18953 https://phaidra.vetmeduni.ac.at/o:605 application/pdf British Journal of Haematology 202(5), 985-994 (2023) British Journal of Haematology 202 5 985 994 21.55 MB 2023