Progression-Free Survival but Not Overall Survival Is Superior in Relapsed/Refractory Large B-Cell Lymphomas Treated with Axicabtagene Ciloleucel Compared to Tisagenlecleucel: Results of the CART-SIE Real Life Italian Study

Introduction The CART-SIE is a national prospective/retrospective observational study aimed at collecting the real-life data of all consecutive lymphoma patients treated with CAR-T cells in the Italian centers. Given the recognized efficacy of axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) in relapsed/refractory large B-cell lymphoma (R/R LBCL) after at least two previous treatments, the best product in terms of efficacy and safety is still a matter of debate. Riedell reported comparable outcomes between axi-cel and tisa-cel in patients treated in 8 US centers; on the other hand, Bachy demonstrated, in a matched comparison, that axi-cel had a higher efficacy and a higher toxicity compared to tisa-cel. Methods On these bases, we conducted a subgroup analysis in the CART-SIE study, with the aim to evaluate the outcome (ORR, DoR, OS, PFS), and the safety (CRS, ICANS) of all R/R LBCL treated with different CAR-T (axi-cel versus tisa-cel) (primary mediastinal B-cell lymphoma, PMBCL, were excluded). A propensity score (PS) model estimated for the probability of being treated with tisa-cel (arbitrary) was performed. Variables used for the PS model (accordingly to Bachy, 2022) were: histology, age, sex, disease status (relapse vs. refractory), Ann Arbor stage (I/II vs. III/IV), IPI (< 3 vs. >=3), LDH, C reactive protein, bulky disease, N of previous treatments, ASCT, bridging therapy (no vs. yes with response vs. yes without response), time since last treatment and centers size (>=25 vs. < 25 cases contributed). Results From March 2019 to June 2023, 659 patients were leukapheresed; 562 were infused and 556 with adequate follow-up were analyzed: 419 LBCL (229 diffuse large B-cell lymphomas, DLBCL; 77 arising from indolent lymphoma, tFL; 113 high-grade B-cell, HGBCL), 70 PMBCL and 67 mantle cell lymphomas. Here, we analyzed the results of the 419 LBCL: 45% (190) received axi-cel, 55% (229) tisa-cel. Clinical characteristics for axi-cel vs. tisa-cel were: median age 57 years (IQR 50;65) vs. 61 (IQR 52;66), p 0.059; refractory to the last treatment 74% (141) vs. 64% (146), p 0.0309; intermediate-high/high risk IPI 39% (74) vs. 46% (105), p 0.1336. Bridging therapy was performed in 82% (156) patients candidate to receive axi-cel and in 85% (195) tisa-cel, p 0.4263; the ORR to bridging was 28% (53) in patients candidate to axi-cel vs. 30% (68) tisa-cel, p 0.1840. All grade CRS was observed in 88% (168) infused with axi-cel, and in 77% (177) with tisa-