18F-FDG PET/CT of off-target lymphoid organs in CD19-targeting chimeric antigen receptor T-cell therapy for relapsed or refractory diffuse large B-cell lymphoma
Thorsten Derlin, Christian Schultze‐Florey, Rudolf A. Werner, Nora Möhn, Thomas Skripuletz, Sascha David, Gernot Beutel, Matthias Eder, Tobias L. Roß, Frank M. Bengel, Arnold Ganser, Christian Koenecke
Abstract
OBJECTIVE: The interplay between systemic inflammation, activity of lymphoid organs and lymphoma activity in CD19-targeting chimeric antigen receptor (CAR)-T-cell immunotherapy, and its significance for response and toxicity, is not well defined. METHODS: F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), metabolic parameters of lymphoma and lymphoid organs were analyzed in ten patients receiving Tisagenlecleucel (an autologous CD19 CAR-T cell product) for relapsed or refractory diffuse large B-cell lymphoma. The prevalence and severity of toxicity (e.g., neurotoxicity) were noted. RESULTS: Achieving remission required early metabolic response (P = 0.0476). Early suppression of metabolic activity of lymphoid organs (spleen, P = 0.0368; lymph nodes, P = 0.0470) was associated with poor outcome. Lymphoma metabolic activity was significantly higher in patients with neurotoxicity (P = 0.0489). CONCLUSIONS: Early metabolic changes in lymphoma lesions and off-target lymphoid organs parallel medium-term response to CAR-T-cell therapy. PET can identify patients at risk for severe toxicity.