Page 246 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 9
More recently, the introduction of chimeric antigen receptor T-cells (CAR-T cell therapy) is of great interest as a new therapy strategy in DLBCL patients since this is a potential curative treatment. There are several different CAR-T therapies in development for lymphoma, most of them targeting the CD19 cell surface protein [31-33]. In short, the idea is that the ex-vivo modified re-infused CAR-T cells will expand in the patients, recognize CD19 positive cells and kill these. The CD19 CAR-T cell therapy (with axicabtagene ciloleucel) is since May 2020 a reimbursed treatment option after 2 or more lines of systemic treatment for relapsed or refractory DLBCL, transformed follicular lymphoma and primary mediastinal B-cell lymphoma in the Netherlands [31,32].
Besides the current role of CAR-T cell therapy in relapsed/refractory DLBCL, clinical trials are ongoing to investigate the role of CD19 targeting CAR-T as part of the frontline therapy in patients with high risk DLBCL. For example, the ZUMA-12 trial in patients with MYC and BCL2 and/or BCL6 (double or triple hit) or IPI>=3 enrolled patients with a positive interim [18F]FDG PET phase II trial are promising, and longer follow-up results are awaited [34].
Other potential interesting “new” therapies that are being investigated are the bispecific monoclonal antibodies [35,36], tandem CAR-T (1 CAR with 2 tumor antigen targets, for example for CD19 and CD20) [37] and combination therapies with other immunomodulatory drugs.
With these new treatment strategies the role and timing of PET response assessment should again be determined for these therapies, bearing in mind that response patterns could be different with immunomodulatory agents [38] and possible criteria refinement could be needed. As these treatment strategies are generally very expensive and probably will be applied to smaller patient groups there is a clear need for defining which patients could benefit from it. For this purpose, both prognostic baseline clinical- (e.g. high IPI) and baseline PET characteristics together with a positive interim [18F]FDG PET could be used to select high risk patients in order to make new clinical trials more efficient.
Future of the PETRA consortium
During the interim [18F]FDG PET lymphoma project, which officially started in January 2015, the PETRA consortium and the PETRA database were established.
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