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

Abstract

Chimeric antigen receptor (CAR) T-cells are a novel immunotherapy available for patients with refractory/relapsed non-Hodgkin lymphoma. In this indication, clinical trials have demonstrated that CAR T-cells achieve high rates of response, complete response, and long-term response (up to 80%, 60%, and 40%, respectively). Nonetheless, the majority of patients ultimately relapsed. This review provides an overview about the current and future role of medical imaging in guiding the management of non-Hodgkin lymphoma patients treated with CAR T-cells. It discusses the value of predictive and prognostic biomarkers to better stratify the risk of relapse, and provide a patient-tailored therapeutic strategy. At baseline, high tumor volume (assessed on CT-scan or on [18F]-FDG PET/CT) is a prognostic factor associated with treatment failure. Response assessment has not been studied extensively yet. Available data suggests that current response assessment developed on CT-scan or on [18F]-FDG PET/CT for cytotoxic systemic therapies remains relevant to estimate lymphoma response to CAR T-cell therapy. Nonetheless, atypical patterns of response and progression have been observed and should be further analyzed. The potential advantages as well as limitations of artificial intelligence and radiomics as tools providing high throughput quantitative imaging features is described.

Whole body FDG PET/MR for progression free and overall survival prediction in patients with relapsed/refractory large B-cell lymphomas undergoing CAR T-cell therapy

“…In addition, a significant cost is currently associated with the treatment. Biomarkers that predict durable response are hence needed, either at baseline to identify patients likely to respond or early post-therapy to detect therapy failure [ 6 ].…”

From Stem Cell Transplantation to CAR-T Therapy in Relapse-Refractory Diffuse Large B-Cell Lymphoma

“…Patients receiving CAR-T with a high tumour burden are at higher risk for treatment failure and shorter survival than those with a low tumour burden. The independent factors predicting relapse and early relapse were the number of extranodal EN sites >2, high CRP, and TMTV >.80 mL; the highest hazard ratio was for the number of extranodal sites >2 and TMTV (33) . This new adverse parameter remains valid for relapsed patients receiving CAR-T therapy.…”

“…Nevertheless, metrics need to be standardized before extending this marker in clinical practice (34) . Baseline high-risk factors, including LDH and ECOG PS (35,33) , inform patient selection pre-CAR-T, but by the time patients have undergone treatment and responded, an individual patient's risk will have changed. On-treatment biomarkers, including imaging markers of response e.g., Deauville score (DS) or disease metabolic volume kinetics (36) , should be incorporated into a dynamic, postinfusion risk model.…”

FDG-PET/CT in Lymphoma: Where Do We Go Now?

“…Interestingly, TMTV seems to represent a promising prognostic tool, as a high tumor volume may correlate with a more severe cytokine release syndrome [71,72]. However, further explorations are needed to confirm these findings.…”