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. 2022 Dec 27;22(1):76.
doi: 10.1186/s40644-022-00513-y.

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

Therese Sjöholm #  1 , Alexander Korenyushkin #  2 , Gustav Gammelgård  3 , Tina Sarén  3 , Tanja Lövgren  3 , Angelica Loskog  3 , Magnus Essand  3 , Joel Kullberg  4   2 , Gunilla Enblad #  3 , Håkan Ahlström #  4   2
Affiliations

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

Therese Sjöholm et al. Cancer Imaging. .

Erratum in

Abstract

Background: To find semi-quantitative and quantitative Positron Emission Tomography/Magnetic Resonance (PET/MR) imaging metrics of both tumor and non-malignant lymphoid tissue (bone marrow and spleen) for Progression Free Survival (PFS) and Overall Survival (OS) prediction in patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL) undergoing Chimeric Antigen Receptor (CAR) T-cell therapy.

Methods: A single-center prospective study of 16 r/r LBCL patients undergoing CD19-targeted CAR T-cell therapy. Whole body 18F-fluorodeoxyglucose (FDG) PET/MR imaging pre-therapy and 3 weeks post-therapy were followed by manual segmentation of tumors and lymphoid tissues. Semi-quantitative and quantitative metrics were extracted, and the metric-wise rate of change (Δ) between post-therapy and pre-therapy calculated. Tumor metrics included maximum Standardized Uptake Value (SUVmax), mean SUV (SUVmean), Metabolic Tumor Volume (MTV), Tumor Lesion Glycolysis (TLG), structural volume (V), total structural tumor burden (Vtotal) and mean Apparent Diffusion Coefficient (ADCmean). For lymphoid tissues, metrics extracted were SUVmean, mean Fat Fraction (FFmean) and ADCmean for bone marrow, and SUVmean, V and ADCmean for spleen. Univariate Cox regression analysis tested the relationship between extracted metrics and PFS and OS. Survival curves were produced using Kaplan-Meier analysis and compared using the log-rank test, with the median used for dichotomization. Uncorrected p-values < 0.05 were considered statistically significant. Correction for multiple comparisons was performed, with a False Discovery Rate (FDR) < 0.05 considered statistically significant.

Results: Pre-therapy (p < 0.05, FDR < 0.05) and Δ (p < 0.05, FDR > 0.05) total tumor burden structural and metabolic metrics were associated with PFS and/or OS. According to Kaplan-Meier analysis, a longer PFS was reached for patients with pre-therapy MTV ≤ 39.5 ml, ΔMTV≤1.35 and ΔTLG≤1.35. ΔSUVmax was associated with PFS (p < 0.05, FDR > 0.05), while ΔADCmean was associated with both PFS and OS (p < 0.05, FDR > 0.05). ΔADCmean > 0.92 gave longer PFS and OS in the Kaplan-Meier analysis. Pre-therapy bone marrow SUVmean was associated with PFS (p < 0.05, FDR < 0.05) and OS (p < 0.05, FDR > 0.05). For bone marrow FDG uptake, patient stratification was possible pre-therapy (SUVmean ≤ 1.8).

Conclusions: MTV, tumor ADCmean and FDG uptake in bone marrow unaffected by tumor infiltration are possible PET/MR parameters for prediction of PFS and OS in r/r LBCL treated with CAR T-cells.

Trial registration: EudraCT 2016-004043-36.

Keywords: ADC; Bone marrow; CAR T-cells; FDG; Immunotherapy; LBCL; PET/MR.

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Conflict of interest statement

JK and HA are co-founders of Antaros Medical AB. GE is a scientific advisor for Elicera Therapeutics AB and XNK Therapeutics AB and a member of the advisory board for Gilead. ME is co-founder and chief scientific officer for Elicera Therapeutics. AL is the CEO of Lokon Pharma AB, chairwoman of Repos Pharma AB and Vivolux AB as well as board member of Lokon Pharma AB, Tanea Medical AB and Aros Bioscience AB. She is alternate board member of Nexttobe AB and Almo Alo AB. Further, she holds a research grant from Lokon Pharma AB.

Figures

Fig. 1
Fig. 1
Example patient scanned over an extended period of time. Maximum Intensity Projection (MIP) SUV images (a, b), axial b900 DW images (c, d) and line graphs of tumor SUVmax and ADCmean quantification over time (e, f). Pre-therapy (t0) and early post-therapy (t1) images are shown in inverted grey scale. A large decrease in MTV between the pre-therapy (MTV = 337 ml) and early post-therapy (MTV = 19 ml) scans was measured, as visualized by the MIP SUV images (a, b). Although this patient had a large total tumor burden pre-therapy, the OS was long (48.2 months with last follow-up as end-point). SUVmax and ADCmean tumor quantification over time (e, f), indicate an intra-tumor heterogenic response to the CAR T-cell therapy. Target lesion selection post-therapy is shown for SUVmax (red arrows) and ADCmean (blue arrows). These tumors are also highlighted in the corresponding color in the line graphs (e, f)
Fig. 2
Fig. 2
Kaplan-Meier survival curves and log-rank p-values for extracted tumor and bone marrow metrics. The median for each metric was used for thresholding. Pre-therapy results (top), showing MTV (a), and bone marrow SUVmean (b,c). Post-therapy rate of change results (bottom) showing ΔMTV (d), ΔTLG (e), and Δ(t1) ADCmean (f, g)
Fig. 3
Fig. 3
Individual bone marrow SUVmean changes between the pre-therapy and 3-week post-therapy scan evaluations. Patients are split according to the median pre-therapy SUVmean of 1.8., with longer PFS and OS observed for patients with higher pre-therapy bone marrow SUVmean. In general, the bone marrow SUVmean decreased post-therapy
See this image and copyright information in PMC

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