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

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 Using serial 18F-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.

[18F]FDG PET-CT in patients with DLBCL treated with CAR-T cell therapy: a practical approach of reporting pre- and post-treatment studies

“…Although other small studies found an association between TT-PET and CRS [20,23], we did not nd association between PET variables at TD or TT and toxicity, possibly because of high prevalence of CRS and small numbers of high-grade CRS and ICANS.…”

“…Several previous studies focused on the role of PET-CT in the mentioned time points [19][20][21][22][23]. In a model built by Vercellino et al for prediction of early progression, total metabolic tumor volume (TMTV) was the only PET parameter assessed.…”

Current and Future Role of Medical Imaging in Guiding the Management of Patients With Relapsed and Refractory Non-Hodgkin Lymphoma Treated With CAR T-Cell Therapy

“…A recent retrospective report on 10 patients with aggressive lymphoma, underlined the importance of early evaluation of therapeutic efficacy, with all patients with a partial or metabolic response at 3 months having shown metabolic response at 1 month, and only one patient with unfavorable outcome experiencing early metabolic response (34).…”

Early Evaluation of Immunotherapy Response in Lymphoma Patients by 18F-FDG PET/CT: A Literature Overview

“…Considering the significance of early PET evaluation for outcome prediction, recently Derlin and colleagues found that, for achieving remission, an early metabolic response at PET was required [ 53 ]. In a pilot study including patients who performed 18F-FDG PET/CT scans before and 1 month after CAR-T-cell therapy, Shah et al demonstrated that all patients that did not reach a complete response subsequently relapsed [ 52 ].…”

“…Immunological mechanisms may also contribute to toxicity, for example with the cytokine release syndrome (CRS), caused by cytokines produced by both activated CAR-T cells and other immune cells [ 68 , 69 ], and the immune effector cell-associated neurotoxicity syndrome (ICANS) [ 52 , 53 , 70 ]. In terms of adverse effects, Whang et al found that higher disease burden, measured by MTV and TLG, was associated with more severe CRS [ 51 , 71 , 72 ].…”