Patient-Derived Lymphoma Spheroids Reveal Predictive Markers of Glofitamab Resistance in Relapsed/Refractory B-NHL.

Using 3D models derived from B-cell lymphoma patient samples, the NoLymit team identified mechanisms of resistance to glofitamab (CD20×CD3), validated through functional approaches. Response was associated with a tumour microenvironment enriched in activated cytotoxic CD8+ T cells, whereas resistance was characterised by exhausted CD8+ T cells and a high abundance of functionally activated T follicular helper (Tfh) cells. Finally, in a subset of patients treated in real life with CD20×CD3 bispecific antibodies, responses measured in PDLS showed a strong correlation with clinical outcomes, suggesting predictive potential.

PDLS paves the way for an ex vivo precision medicine platform, combining the prediction of response to bispecific antibodies with the identification of stratification biomarkers to help stratify patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma.

Outlook: Personalised medicine, prospects for new treatment combinations

Collaborations and partnerships

Collaborations :

• CHU Toulouse, Institut Claudius Regaud-UCT-Oncopole, France
• Dpt of Hematology, Oncology and Clinical Immunology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
• Spatial and Functional Screening Core Facility, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany
• European Molecular Biology Laboratory (EMBL) Heidelberg, Heidelberg, Germany
• Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany
• Department of Medicine V, Heidelberg University Hospital, Heidelberg, Germany
• Fundació Clínic per a la Recerca Biomèdica – Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
• Centro de Investigación Biomédica en Red-Oncología (CIBERONC), Madrid, Spain.
• F.Hoffmann-La Roche, Basel, Switzerland.
• Roche Pharma Research and Early Development, Roche Innovation Center Zürich, Schlieren, Switzerland.
• Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche U1236, Université Rennes, Etablissement Français du Sang Bretagne, LabEx IGO, Rennes, France.
• Department of Hematology, University Hospital of Lyon, Lyon, France
• Institut de Génétique Humaine, Centre Hospitalier Universitaire, Montpellier, France.
• Clinical Haematology Dijon University Hospital Dijon France.
• Department of Hematology, Univ. Grenoble-Alpes, CHU Grenoble Alpes, Grenoble, France,
• Department of Hematology, CHU Lille, Lille, France.
• Department of Clinical Hematology, CHU Montpellier, Montpellier, France

Fouding :

• F. Hoffmann-La Roche Ltd,
• imCORE,
• European TRANSCAN program,
• Labex TOUCAN,
• INSERM,
• Université de Toulouse
• CALYM Carnot Institute.