Cart‐sie real life study: primary mediastinal b‐cell lymphoma (pmbcl) have a superior outcome compared to large b‐cell lymphoma (lbcl) treated with axicabtagene ciloleucel

Introduction: In Italy, axicabtagene ciloleucel (axi-cel) is commercially available for the treatment of LBCL, including diffuse large B-cell lymphoma (DLBCL-NOS), high grade B-cell lymphoma (HGBCL), transformed follicular lymphoma (tFL), and PMBCL patients, relapsed/refractory (R/R) after at least two prior treatments. Methods: The CART-SIE is an ongoing prospective and retrospective study collecting data on the outcome of all consecutive lymphoma patients treated with CAR-T cells. The aim of this analysis was to compare the outcome of PMBCL and LBCL treated with axi-cel in the Italian real life. Results: From 2019 to 2022, 444 patients were infused. Axi-cel was administered in 192 patients: 57 PMBCL and 135 LBCL, including DLBCL-NOS (85), HGBCL (28) and tFL (22), respectively. The clinical characteristics for PMBCL versus LBCL showed: median age 35 versus 56 (p = 0.0001), bulky 33/57 (58%) versus 47/135 (35%) (p = 0.0035), limited stage 35/57 (61%) versus 41/135 (31%) (p = 0.0001), respectively. Median follow-up time for infused patients was 10.99 months (IQR 4.18, 18.03). The Overall Response Rate (ORR, complete CR + partial PR) at 30-days after the infusion was 44/57 (77%) with 30 (53%) CR in PMBCL, and 97/135 (72%) with 67 (50%) CR in LBCL, (p = 0.4206). The 12-months Overall Survival (OS) was 89% (95% CI: 81–98) in PMBCL versus 70% (95% CI: 62–80) in LBCL (log-rank p = 0.0016); by different histology subtypes, the 12-months OS was 89% (95% CI: 81–98) in PMBCL versus 74% (95% CI: 63–86) in DLBCL-NOS, 58% (95% CI: 41–81) in HGBCL, 76% (95% CI: 58–100) in tFL (log-rank p = 0.0013). The 12-months PFS was 65% (95% CI: 53–80) in PMBCL versus 47% (95% CI: 39–57) in LBCL (log-rank p = 0.0160); by different histology subtypes, the 12-months PFS was 65% (95% CI: 53–80) in PMBCL versus 40% (95% CI: 30–54) in DLBCL-NOS, 51% (95% CI: 35–75) in HGBCL, 65% (95% CI: 47–90) in tFL (log-rank p = 0.0420). All grades CRS was observed in 49/57 (86%) PMBCL and 118/135 (87%) LBCL patients, with 9 (16%) and 12 (9%) severe (grade 3–4) CRS, respectively; all grades ICANS were reported in 25 (44%) PMBCL patients and in 46 (34%) LBCL, with 12 (21%) and 14 (10%) severe (grade 3–4) ICANS, respectively. Tocilizumab was administered in 41 (72%) PMBCL and in 90 (67%) LBCL; steroids in 20 (35%) PMBCL and in 36 (27%) LBCL patients. Twelve (21%) PMBCL and 15 (11%) LBCL patients were admitted in the intensive care unit. Treatment related mortality was reported in 3 (5%) PMBCL and 3 (2%) LBCL patients. In a multivariable model with all clinically important and unbalanced variables, PMBCL maintained its significantly superior outcome as compared to LBCL, for OS and for PFS. Conclusions: CART-SIE is the first real-life study comparing the prognosis of patients affected by R/R PMBCL and LBCL treated with axi-cel. PMBCL patients had a superior OS and PFS compared to LBCL, with a similar incidence of CRS and ICANS. Encore Abstract—previously submitted to EHA 2023 Keywords: aggressive B-cell non-Hodgkin lymphoma, cellular therapies Conflicts of interests pertinent to the abstract A. Chiappella Consultant or advisory role: Celgene-BMS, Gilead-Sciences, Ideogen, Janssen, Roche, SecuraBIO, Takeda Other remuneration: Lecture fees/Educational activities: Astrazeneca, Celgene-BMS, Gilead-Sciences, Incyte, Janssen-Cilag, Novartis, Roche, Takeda