Abstract
2719
Introduction: Objectives: 1. To review recent literature on the usage of [18F]fluorodeoxyglucose ([18F]FDG) PET and global assessment to evaluate and quantify response to chimeric antigen receptor (CAR) T cell therapy. 2. To emphasize the role of [18F]FDG-PET in predicting patient outcomes due to its inherent avidity to cancer cells.
Methods: Research databases, including Google Scholar and PubMed, were searched to compile literature relevant to CAR-T cell therapy response as measured by [18F]FDG-PET. Studies that attempted to predict patient outcomes with [18F]FDG-PET were preferred. Others that measured the outcomes of multiple CAR-T cell therapies were added for relapse rates and other background information.
Results: Assessing treatment response has been difficult in cancer treatment, especially with CAR-T cell therapy. Quick and almost complete responses can result in relapses despite initial successes. Accurately predicting patient outcomes for better treatment planning and limitation of unnecessary treatment is needed. An ideal method could differentiate between “false” early success and later complete treatment response. The continued development of new CAR-T cell therapies, including treatments for specific types of leukemia or lymphoma, would benefit from such a method. [18F]FDG-PET is the foremost technology to accomplish this goal. Investigators indicate for example that the presence of extranodal lesions are highly correlative to early relapse and death in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL), which are more easily identified with the help of highly specific [18F]FDG-PET. Total lesion glycolysis (TLG) and metabolic tumor volume (MTV) are two parameters that [18F]FDG-PET is able to measure for tumor burden. They have been shown to have prognostic value in chemotherapy and radiation therapy treatments. One study found that it was possible to differentiate between responders and nonresponders to CAR-T cell therapies in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) using standard uptake value maximum (SUVmax) one month after CAR-T cell introduction compared to the baseline SUVmax. A second study confirmed the usefulness of [18F]FDG-PET early in treatment where MTV changes can later correspond with longer term response to the therapy.
[18F]FDG-PET has also been shown to predict adverse effects of treatment, for example cytokine release syndrome (CRS), a serious concern for patients receiving immunotherapy treatments. CRS is potentially fatal and can require a ventilator and other devices upon severe disease progression. One non-Hodgkin lymphoma (NHL) study found that higher initial disease burden, as measured by [18F]FDG-PET through TLG and MTV parameters, correlated with more serious CRS as well as a pseudoprogression of lymphomas, which could otherwise confound image interpretations. A R/R DLBCL study similarly affirmed the ability of [18F]FDG-PET to predict patients’ likelihood for serious toxicity concerns as a result of treatment.
Conclusions: Given the prognostic value of [18F]FDG-PET for other cancer therapies, more research is merited for CAR-T cell prognostication. Having a predictive tool that is highly specific can accelerate the production of new CAR-T cell therapies and ensure that patients are receiving a course of treatment to which they will be responsive. The recent literature on [18F]FDG-PET usage for CAR-T cell therapy evaluation has emphasized its benefit for prognostication and quantification of treatment response. In addition, [18F]FDG-PET serves as a valuable tool which can be applied to selection of patients for CAR-T cell treatments based on the risk of complications due to CRS and neurotoxicity. The most effective method to determine patient risk of toxicity, overall survival rate, and treatment response is likely [18F]FDG-PET quantification of tumor activity and global assessment.