P1081: a multicenter observational study on chimeric antigen receptor t-cell therapy for large b-cell (lbcl) and mantle cell (mcl) lymphomas: the italian cart-sie real life experience

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: Axi-cel and Tisa-cel are reimbursed in Italy for the treatment of relapsed/refractory (R/R) LBCL, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), and high-grade B-cell lymphoma (HGBCL) after at least two treatment lines. Brexu -cel is commercially available in R/R mantle cell lymphoma (MCL) failing a BTK inhibitor. Aims: The aim of this analysis was to evaluate outcome [overall response rate (ORR), overall survival (OS), progression free survival (PFS)], and safety [cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS)] of the different CAR-T products in the Italian real life setting. Methods: The CART-SIE is a national ongoing prospective and retrospective observational study collecting the data of all consecutive lymphoma patients treated with CAR-T cells in the Italian centers. Results: From March 2019 to December 2022, 499 patients were enrolled and leukapheresed; 444 patients were infused (89%) and 426 with adequate follow-up were included into this analysis. Clinical characteristics of the 426 patients were as follows: median age 57 years (IQR: 46-65), stage III/IV 300 (70%); median number of prior lines was 2 (IQR: 2-3), and 295 (69%) were refractory to the last treatment. According to local pathology reports, 44 (10%) were MCL and 382 (90%) LBCL, including 236 (55%) DLBCL, 89 (21%) HGBCL, 57 (13%) PMBCL. Bridging therapy was delivered to 343 (81%) patients. Median follow-up time for infused patients was 10.99 months (IQR: 4.18-18.03). Brexu-cel was infused in 43/44 (98%) MCL patients; the ORR at 30-days was 33/44 patients (75%), with 24 (56%) CRs; the 12-months OS was 76% (95% CI: 56-100) and the 12-months PFS was 59% (95% CI: 35-97). In the 382 LBCL, axi-cel was infused in 192 (50%), and tisa-cel in 190 (50%) patients; the ORR at 30-days was 255/ 382 (67%) patients, with 174 (46%) CRs; the 12-months OS was 71% (95% CI: 66-76) and the 12-months PFS was 45% (95% CI: 39-50). By histotype, the 12-months OS was 89% (95% CI: 81-98) in PMBCL, 70% (95% CI: 64-78) in DLBCL, 58% (95% CI: 47-71) in HGBCL, and the 12-months PFS was 65% (95% CI: 53-80) in PMBCL, 42% (95% CI: 35-50) in DLBCL, 38% (95% CI: 29-50) in HGBCL, respectively. In the whole population, all grade CRS was observed in 355/426 (83%) patients, with 47 (11%) severe (grade 3-4); ICANS in 103 (24%) patients, with 39 (9%) severe (grade 3-4). Tocilizumab was administered in 272 (64%) and steroids in 108 (25%) patients; 46 patients (11%) were admitted in the intensive care unit. Treatment related mortality was recorded in 9 (2%) patients. CAR-T expansion kinetics was assessed in a cohort of 150 patients with a positive correlation with response and survival (p-value 0.0076 and 0.036 respectively). A sub-analysis comparing axi-cel and tisa-cel was performed in the DLBCL and HGBCL cases, excluding The two cohort of patients were unbalanced for several variables (table 1). Keeping in mind these limitations, no differences between axi-cel and tisa-cel were reported in OS: 12-months OS 71% (95% CI: 62-80) and 64% (95% CI: 56-73) (log-rank p=0.6792); an advantage of axi-cel compared to tisa-cel was observed in PFS: 12-months PFS 47% (95% CI: 38-57) and 37% (95% CI: 30-45), respectively (log-rank p=0.0354). Summary/Conclusion: In CART-SIE study, the outcomes of patients treated with CAR-T were similar to those reported by pivotal trials and real life studies. CRS and ICANS in real world are controllable with an adequate risk management plan. Outcomes OS was similar for axi-cel and tisa-cel patients, but an advantage in term of PFS was observed for axi-cel-treated patients. This results could be influenced by the differences between the two groups of patients, that are unbalanced for histotypes and disease status.Keywords: CAR-T, Real world data, Diffuse large cell lymphoma, Mantle cell lymphoma