S228: positron emission tomography evaluation in a large group of patients affected by relapsed/refractory b-cell lymphomas treated with anti-19 chimeric antigen receptor (car) t-cells therapy (cart sie).

Background: CD19 direct chimeric antigen receptor (CAR) T-cell therapy is an effective therapy for patients (pts) affected by relapsed/refractory (R/R) large B-cell lymphomas (LBCL). Positron emission tomography/computed tomography (PET/CT) is used early post CAR T-infusion but the prognosis of pts with partial or stable disease at 1-month is less define. Aims: The objective of the study was to analyze the role of early PET/CT in combination with pre-infusion biomarkers to determine long-term outcome. Methods: CART-SIE is an ongoing prospective and retrospective observational study evaluating the outcome of pts treated with CAR T-cells. From March 2019 to December 2022, 499 patients were enrolled. In this study we included only pts with adequate follow-up (30 days) and an FDG-PET/CT before infusion (PET-0), at 1 month (PET-1) and at 3 months (PET-3) after CAR-T cells infusion. A landmark analysis based on PET-1 result was performed for Progression-free survival (PFS) and Overall Survival (OS) estimation. Results: Two hundred and twenty-one pts with R/R LBCL [n= 129 Diffuse large B-cell lymphomas, n= 39 High-grade B-cell lymphomas (HGBCL), n= 27 Primary Mediastinal B-cell lymphomas (PMBCL), n= 26 Mantle Cell Lymphoma (MCL)] received CAR T-cell treatment with axicabtagene-ciloleucel (n=103, axicel), tisagenlecleucel (n=93, tisacel) and brexucabtagene autoleucel (n=25, brexucel). The median age of the pts was 57 years (64 pts were older of 65 years). Most of the pts [n=184(83%)] were treated with a bridging therapy. Bulky and extranodal disease were observed in 72(32%) and 125(56%) of the pts, respectively. Evaluation of pre-lymphocytoapheresis absolute lymphocyte value and PCR were evaluable for 199 (90%) and 183 (83%) pts, respectively. The median follow-up time was 11 months. At the time of PET-1, 116 pts (52%) showed a PET with DS1-3, 52 (24%) had a PET with DS 4 (n=38 PR, n=14 SD) and 53 (24%) with DS5 (n=16 SD, n=37 PD). At the time of PET-3, 11 of 52 (21%) DS4 and 3 of 53 (6%) DS5 at PET-1 converted in CR. The 1-year PFS based on PET-1 was 67%, 42% and 8% for DS1-3, DS4 and DS5 (p<0,0001), respectively. The 1-year OS based on PET-1 was 90%, 83% and 37% for DS1-3, DS4 and DS5, respectively. Multivariable analyses identified DS5 value at day 30 and CAR T-cell product Tisacel associated to increase risk of failure (HR: 11.03; 95%CI 5.47-22.21, p<0.0001; 1.79; 95%CI: 0.98-3.27; p<0.0586) whereas higher lymphocyte count at lymphocytoapheresis improved outcome (HR: 0.65; 95%CI: 0.46-0.90; p<0.0101). Summary/Conclusion: The 1-year PFS of pts with DS4 at PET-1 was only 42% suggesting the need of early salvage treatment in these pts and integration with biological markers to help in predicting the progression risk; pts with DS5 had a very poor outcomeKeywords: Positron emission tomography (PET), CAR-T