Positron emission tomography-imaging assessment for guiding strategy in patients with relapsed/refractory large B-cell lymphoma receiving CAR T cells

Abstract

The aim of this study was to evaluate the prognostic impact of the F-fluorodeoxyglucose positron emission tomography response at 1 month (M1) and 3 months (M3) after anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in a multicenter cohort of 160 patients with relapsed/refractory large B-cell lymphomas (R/R LBCL). In total, 119 (75%) patients reached M1 evaluation; 64 (53%, 64/119) had a complete response (CR); 91% were Deauville Score (DS) 1-3. Progressionfree survival (PFS) and overall survival (OS) were significantly worse in patients with DS-5 at M1, than in patients with DS 1-3 (PFS hazard ratio [HR]=6.37, 95% confidence interval [CI]: 3.5-11.5 vs. OS HR=3.79, 95% CI: 1.7-8.5) and DS-4 (PFS HR=11.99, 95% CI: 5.0-28.9 vs. OS HR=12.49, 95% CI: 2.8-55.8). The 1-year PFS rates were 78.9% (95% CI: 58.9-89.9) for DS-4 at M1, similar to 67.3% (95% CI: 51.8-78.8) for patients with DS 1-3 at M1, very different to 8.6% (95% CI: 1.8-22.4) for DS-5, respectively. Only eight of 30 (26%) patients with DS-4 progressed. Response at M3 evaluated in 90 (57%) patients was prognostic for PFS with lower discrimination (HR=3.28, 95% CI: 1.5-7.0; P=0.003) but did not predict OS (HR=0.61, 95% CI: 0.2-2.3; P=0.45). Patients with a high baseline total metabolic tumor volume (TMTV) >80 mL had worse PFS (HR=2.05, 95% CI: 1.2-3.5; P=0.009) and OS (HR=4.52, 95% CI: 2.5-8.1; P<0.001) than patients with low TMTV. Multivariable analyses identified baseline elevated lactate dehydrogenase, DS-5, CAR T cells at M1 for PFS and baseline elevated lactate dehydrogenase, TMTV >80 mL, and DS-5 at M1 for OS. In conclusion, baseline TMTV and response at M1 strongly predicts outcomes of patients with R/R LBCL undergoing CAR T-cell therapy.

Liver-FDG-uptake and CAR T-cell kinetics augment early PET/CT prognostic value for CD19-targeted CAR T-cell therapy in diffuse large B cell lymphoma

“…Offering the possibility of early intervention following CD19.CAR-T in aggressive lymphoma, PET30 has recently evolved as a strong predictor for lasting remission (29,41). However, high rates of false-positive and false-negative prediction by PET30 are a problem.…”

“…Early after CAR-T cell infusion, absolute CAR-T cell levels greater than 19 / µl (24)or 20 /µl (25) at day seven to 10 or complete metabolic response at day 30 by PET/CT (PET30-CR) robustly predicted long-term outcome (26)(27)(28). Though PET/CT imaging is the most precise method to evaluate responses in aggressive lymphoma (26), up to 30% of patients do not achieve long-term remission despite PET30-CR (false-negative prediction) and relapse within 12 months from CAR-T cell infusion (28,29). Similarly, early CAR-T cell expansion produces false-positive and false-negative prediction of PFS (24).…”

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

“…[ 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 …”

“…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 .…”

“…[ 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.…”