Early positron emission tomography/computed tomography as a predictor of response after CTL019 chimeric antigen receptor –T-cell therapy in B-cell non-Hodgkin lymphomas

• Published in: Cytotherapy (Oxford, England) England), 2018-12, Vol.20 (12), p.1415-1418
• Main Authors: Shah, Nirav N, Nagle, Sarah J, Torigian, Drew A, Farwell, Michael D, Hwang, Wei-Ting, Frey, Noelle, Nasta, Sunita D, Landsburg, Daniel, Mato, Anthony, June, Carl H, Schuster, Stephen J, Porter, David L, Svoboda, Jakub
• Format: Article
• Language: English
• Subjects: 18F-Fluorodeoxyglucose positron emission tomography/computed tomography; Advanced Basic Science; immunotherapy; lymphoma; Other; response assessment
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2018.10.003

Abstract Molecular imaging with18 F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is an established modality for response assessment in patients with lymphoma undergoing treatment. However, patients treated with novel immunotherapies may have false-positive PET/CT findings due to tumor site and systemic inflammation. In particular, treatment with autologous chimeric antigen receptor modified T-cells redirected at CD19 (CTL019 CAR-T cells) is often complicated by “cytokine release syndrome” (CRS) due to a severe systemic inflammatory reaction. Infiltration of tumors by activated CTL019 cells may impact radiographic and functional imaging findings. The role of PET/CT in patients treated with CTL019 has not previously been described. We performed a pilot, single-arm, prospective study to explore the utility of early PET/CT in patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) undergoing treatment with CTL019 CAR-T cells. Patients had PET/CT prior to CTL019 infusion and then early PET/CT at 1 month after treatment. The primary outcome was the amount/change in metabolically active tumor volume (MTV) and FDG uptake. We enrolled seven patients (DLBCL, three; FL, four). Six of 7 had baseline PET/CT with active disease. On post-treatment PET/CT, three patients had no residual MTV, two patients had a decrease in MTV and two patients had an increase in MTV. The three patients with no residual MTV all remain in remission >2 years post-treatment. The patients with less than complete response all subsequently relapsed. Development of CRS did not confound PET/CT findings. In patients with DLBCL and FL receiving CTL019 CAR-T cells, early PET/CT may predict response to this novel immunotherapy.