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

Nirav N Shah; Sarah J Nagle; Drew A Torigian; Michael D Farwell; Wei-Ting Hwang; Noelle Frey; Sunita D Nasta; Daniel Landsburg; Anthony Mato; Carl H June; Stephen J Schuster; David L Porter; Jakub Svoboda

doi:10.1016/j.jcyt.2018.10.003

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

Cytotherapy. 2018 Dec;20(12):1415-1418. doi: 10.1016/j.jcyt.2018.10.003. Epub 2018 Oct 29.

Authors

Affiliations

¹ Medical College of Wisconsin, Division of Hematology/Oncology, Milwaukee, Wisconsin, USA. Electronic address: nishah@mcw.edu.
² Center for Hematologic Malignancies, The Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
³ Department of Radiology, Hospital of the University of Pennsylvania, Pennsylvania, USA.
⁴ Lymphoma Program at the Abramson Cancer Center and the Division of Hematology-Oncology Perelman School of Medicine, University of Pennsylvania, Pennsylvania, USA.
⁵ Memorial Sloan Kettering Cancer Center, New York, New York, USA.
⁶ Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁷ Lymphoma Program at the Abramson Cancer Center and the Division of Hematology-Oncology Perelman School of Medicine, University of Pennsylvania, Pennsylvania, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

PMID: 30385043
DOI: 10.1016/j.jcyt.2018.10.003

Abstract

Molecular imaging with ¹⁸F-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.

Keywords: (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography; immunotherapy; lymphoma; response assessment.

Publication types

Letter