Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Predicting the Adverse Effects of Chimeric Antigen Receptor T Cell Therapy in Patients with Non-Hodgkin Lymphoma

Abstract

CD19-targeting chimeric antigen receptor (CAR)-T cell therapy has shown great efficacy in patients with relapsed/ refractory non-Hodgkin lymphoma (NHL) but has been associated with serious adverse effects, such as cytokine release syndrome (CRS). It has been speculated that NHL baseline disease burden might affect clinical outcome and CRS, but this has not been explored in detail in any previous study. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as measured by fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT), are quantitative indicators of baseline tumor burden. Using FDG PET-CT, we calculated baseline and post-CAR-T cell therapy MTV and TLG in 19 patients with NHL. The median MTV was 72 cm 3 (range, .02 to 1137.7 cm 3 ), and the median TLG was 555.9 (range, .011 to 8990.3). After a median follow-up of 5 months (range, 1 to 12 months), the best overall response rate was 79.0%. The baseline MTV and TLG did not differ significantly between patients with response and those without response (P = .62 and .95, respectively). On Cox regression analysis, baseline MTV and TLG were not significantly associated with overall survival (P = .67 and .45, respectively). Patients with mild and moderate CRS (grade 0 to 2) had significantly lower MTV and TLG than those with severe CRS (grade 3 to 4) (P = .008 for MTV comparison, P = .011 for TLG comparison). Using FDG PET-CT, we also demonstrated that CAR-T cell therapy in patients with NHL was associated with pseudoprogression and local immune activation. Our data indicate that patients with higher baseline disease burden have more severe CRS, and that CAR-T cell therapy is associated with lymphoma pseudoprogression and local immune activation.

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

“…We did not note any noticeable changes in brain metabolism in patients having experienced neurotoxicity, and PET was performed at a later time point (Day 30) in this study. In a study including 19 patients, Wang et al reported that patients with higher baseline disease burden as determined by FDG PET (both baseline MTV and TLG) had more severe CRS [15]. We did not observe a significant association with disease burden in a smaller patient cohort.…”

Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma

“…Using the TMTV41% method, the optimal threshold for early relapse, in terms of false-positive and false-negative predictions, in our series was 80 mL. The putative prognostic impact of TMTV in patients treated with CAR T cells has been suggested in a series of only 19 patients, 21 in which TMTV tended to be lower in responding patients. Interestingly, median TMTV in this study was 72 mL and, thus, very close to our own data.…”

Extranodal site of diffuse large B‐cell lymphoma and the risk of R‐CHOP chemotherapy resistance and early relapse

“…The novel CAR‐T cells therapy has shown great efficacy in RR‐RCHOP DLBCL patients. The drawback of this therapy is patients may develop “cytokine release syndrome” which could cause false positive results on PET/CT scans 43 . Nevertheless, an explorative study on patients treated with CAR‐T cells therapy showed that “cytokine release syndrome” does not confound post‐treatment PET/CT scan findings.…”