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

Sjöholm, Therese; Korenyushkin, Alexander; Gammelgård, Gustav; Sarén, Tina; Lövgren, Tanja; Loskog, Angelica; Essand, Magnus; Kullberg, Joel; Enblad, Gunilla; Åhlström, Håkan

doi:10.1186/s40644-022-00513-y

Cited by 8 publications

(6 citation statements)

References 57 publications

(78 reference statements)

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“…[ 18 F]‐Fluorodeoxyglucose (FDG)‐PET has a well‐recognized role in the staging, restaging, and therapy response assessment in patients with lymphomas including patients candidate for or treated with CAR‐T 17–25 …”

Section: Introductionmentioning

confidence: 99%

“…At present, both in trials and clinical practice, whole‐body [ 18 F]FDG PET is performed before and around 30 days after treatment with CAR‐T 1,17–25 . Preliminary data have linked the metabolically active tumor burden as measured with PET with the risk of developing CRS 24–26 .…”

Section: Introductionmentioning

confidence: 99%

“…[ 18 F]-Fluorodeoxyglucose (FDG)-PET has a well-recognized role in the staging, restaging, and therapy response assessment in patients with lymphomas including patients candidate for or treated with CAR-T. [17][18][19][20][21][22][23][24][25] At present, both in trials and clinical practice, whole-body [ 18 F]FDG PET is performed before and around 30 days after treatment with CAR-T. 1,[17][18][19][20][21][22][23][24][25] Preliminary data have linked the metabolically active tumor burden as measured with PET with the risk of developing CRS. [24][25][26] In particular, it has been suggested that patients with higher baseline metabolic tumor volume (MTV) may have more severe CRS.…”

Section: Introductionmentioning

confidence: 99%

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Brain FDG‐PET findings in chimeric antigen receptor T‐cell therapy neurotoxicity for diffuse large B‐cell lymphoma

Morbelli

Gambella

Raiola

et al. 2023

Journal of Neuroimaging

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Background and PurposeChimeric antigen receptor (CAR) T‐cell therapy is potentially associated with treatment‐related toxicities mainly consisting of cytokine release syndrome (CRS) and immune‐effector cell‐associated neurotoxicity syndrome (ICANS). We evaluated brain metabolic correlates of CRS with and without ICANS in diffuse large B‐cell lymphoma patients treated with CAR‐T.MethodsTwenty‐one refractory DLCBLs underwent whole‐body and brain [18F]‐fluorodeoxyglucose (FDG) PET before and 30 days after treatment with CAR‐T. Five patients did not develop inflammatory‐related side effects, 11 patients developed CRS, while in 5 patients CRS evolved in ICANS. Baseline and post‐CAR‐T brain FDG‐PET were compared with a local controls dataset to identify hypometabolic patterns both at single‐patient and group levels (p < .05 after correction for family‐wise error [FWE). Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were computed on baseline FDG‐PET and compared between patients’ subgroups (t‐test).ResultsICANS showed an extended and bilateral hypometabolic pattern mainly involving the orbitofrontal cortex, frontal dorsolateral cortex, and anterior cingulate (p < .003 FWE‐corrected). CRS without ICANS showed significant hypometabolism in less extended clusters mainly involving bilateral medial and lateral temporal lobes, posterior parietal lobes, anterior cingulate, and cerebellum (p < .002 FWE‐corrected). When compared, ICANS showed a more prominent hypometabolism in the orbitofrontal and frontal dorsolateral cortex in both hemispheres than CRS (p < .002 FWE‐corrected). Mean baseline MTV and TLG were significantly higher in ICANS than CRS (p < .02).ConclusionsPatients with ICANS are characterized by a frontolateral hypometabolic signature coherently with the hypothesis of ICANS as a predominant frontal syndrome and with the more prominent susceptibility of frontal lobes to cytokine‐induced inflammation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Brain FDG‐PET findings in chimeric antigen receptor T‐cell therapy neurotoxicity for diffuse large B‐cell lymphoma

Morbelli

Gambella

Raiola

et al. 2023

Journal of Neuroimaging

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“…Although tumor burden is a critical factor influencing the success of CAR T therapy (13)(14)(15), the presence of disseminated tumor already serves as a primary exclusion criterion for this treatment. Some researchers propose that assessing the tumor burden prior to CAR T cell therapy may predict therapy's outcome (14,16,17). However, given the stringent inclusion criteria and the complex mechanisms affecting the therapy's outcome and the onset of side effects, this strategy alone is not comprehensive enough for effective prediction of therapy progression (18).…”

Section: Introductionmentioning

confidence: 99%

Biomarkers for prediction of CAR T therapy outcomes: current and future perspectives

Levstek,

Janžič,

Ihan

et al. 2024

Front. Immunol.

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Chimeric antigen receptor (CAR) T cell therapy holds enormous potential for the treatment of hematologic malignancies. Despite its benefits, it is still used as a second line of therapy, mainly because of its severe side effects and patient unresponsiveness. Numerous researchers worldwide have attempted to identify effective predictive biomarkers for early prediction of treatment outcomes and adverse effects in CAR T cell therapy, albeit so far only with limited success. This review provides a comprehensive overview of the current state of predictive biomarkers. Although existing predictive metrics correlate to some extent with treatment outcomes, they fail to encapsulate the complexity of the immune system dynamics. The aim of this review is to identify six major groups of predictive biomarkers and propose their use in developing improved and efficient prediction models. These groups include changes in mitochondrial dynamics, endothelial activation, central nervous system impairment, immune system markers, extracellular vesicles, and the inhibitory tumor microenvironment. A comprehensive understanding of the multiple factors that influence therapeutic efficacy has the potential to significantly improve the course of CAR T cell therapy and patient care, thereby making this advanced immunotherapy more appealing and the course of therapy more convenient and favorable for patients.

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“… 21 Furthermore, higher pretreatment MTV was associated with poorer clinical outcomes in patients receiving anti-CD19 CAR T-cell therapy for R/R LBCL after ≥2 lines of therapy. 22 , 23 , 24 , 25 , 26 Here, we present exploratory analyses of relationships between whole-body MTV at baseline and clinical outcomes for patients treated with axi-cel or standard care in the ZUMA-7 study.…”

Section: Introductionmentioning

confidence: 99%

Axicabtagene ciloleucel vs standard of care in second-line large B-cell lymphoma: outcomes by metabolic tumor volume

Locke,

Oluwole,

Kuruvilla

et al. 2024

Blood

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Metabolic tumor volume (MTV) assessed using 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography, a measure of tumor burden, is a promising prognostic indicator in large B-cell lymphoma (LBCL). This exploratory analysis evaluated relationships between baseline MTV (categorized as low [≤median] vs high [>median]) and clinical outcomes in the phase 3 ZUMA-7 study (NCT03391466). Patients with LBCL relapsed within 12 months of or refractory to first-line chemoimmunotherapy were randomized 1:1 to axicabtagene ciloleucel (axi-cel; autologous anti-CD19 chimeric antigen receptor [CAR] T-cell therapy) or standard care (2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation in patients who had a response). All P values are descriptive. Within high and low MTV subgroups, event-free survival (EFS) and progression-free survival (PFS) were superior with axi-cel vs standard care (all HR ≤0.523; P<.01). EFS in patients with high MTV (vs low MTV) was numerically shorter with axi-cel (HR, 1.448; P=.06) and was significantly shorter with standard care (HR, 1.486; P=.02). PFS was shorter in patients with high MTV vs low MTV in both the axi-cel (HR,1.660; P=.02) and standard-care (HR, 1.635; P=.02) arms, and median MTV was lower in patients in ongoing response at data cutoff vs others (both P≤.01). Median MTV was higher in axi-cel-treated patients who experienced grade ≥3 neurologic events or cytokine release syndrome (CRS) than in patients with grade 1/2 or no neurologic events or CRS, respectively (both P≤.03). Baseline MTV ≤median was associated with better clinical outcomes in patients receiving axi-cel or standard care for second-line LBCL.

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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

Cited by 8 publications

References 57 publications

Brain FDG‐PET findings in chimeric antigen receptor T‐cell therapy neurotoxicity for diffuse large B‐cell lymphoma

Brain FDG‐PET findings in chimeric antigen receptor T‐cell therapy neurotoxicity for diffuse large B‐cell lymphoma

Biomarkers for prediction of CAR T therapy outcomes: current and future perspectives

Axicabtagene ciloleucel vs standard of care in second-line large B-cell lymphoma: outcomes by metabolic tumor volume

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