Feng, Zhongyu

7028 Background: Axi-cel, autologous anti-CD19 CAR T-cell therapy, showed long-term survival and curative potential in R/R LBCL (ZUMA-1; Neelapu et al. Blood . 2023). Few studies have examined long-term outcomes beyond clinical trials. Here we report long-term real-world outcomes of axi-cel in R/R LBCL using large-sample CIBMTR data. Methods: A total of 1500 adults from 79 US centers receiving commercial axi-cel after ≥2 LOT for LBCL from Oct 2017-Aug 2020 were enrolled in a post-marketing requirement study. A protocol was developed prior to the study’s implementation, reviewed by Kite and CIBMTR. This is a secondary analysis of said study. Key outcomes were progression-free survival (PFS), overall survival (OS), time to next therapy (TTNT), disease-specific mortality (competing risks were non-relapse deaths), subsequent malignancies, and non-relapse mortality (NRM). Outcomes were analyzed descriptively. Cases with missing data were excluded separately for each endpoint. Results: As of Aug 2025, 1446 patients (pts) were included in the analysis. Median age at infusion was 62.2 y (range, 19.6-90.8: 38% of pts ≥65 y); 65% were male. Five percent of pts had ECOG PS ≥2 and 16% had high-grade lymphoma. Pts had a median of 3 (range, 2-4) prior LOT, 28% had prior autologous hematopoietic cell transplantation, and 50% received bridging therapy. At 59.7 mo median follow-up, median PFS (95% CI) was 7.9 mo (6.3-10.9) and 5-y PFS was 30% (27-32). The median OS was 25.7 mo (21.6-30.2); 5-y OS was 38% (35-41). The 5-y cumulative incidence of disease-specific mortality was 51%. Among pts who were progression-free at 2, 3, 4, or 5 y post-infusion, the OS at 6 y (95% CI) was 73% (68-78), 81% (76-86), 90% (84-94), and 94% (89-97), respectively. The median duration of response (DOR) was 25.3 mo (95% CI, 20.7-32.8) and 5-y DOR was 38% (35-41). The median TTNT was 12.2 mo and 30% did not need additional LOT at 5 y. Of pts who received subsequent salvage therapy, 12 (2%) received cell therapy, 39 (7%) received hematopoietic cell transplant, and 475 (90%) received other therapy. The 1, 2, 3, 4, and 5-y cumulative incidence of relapse (95% CI) was 49% (46-51), 52% (50-55), 54% (52-57), 55% (53-58), and 56% (53-59), respectively. No new safety signals were observed. The primary causes of death (n=864; 60%) were primary disease (540; 63%), infection (111; 13%), and organ failure (57; 7%). The 5-y cumulative incidence of NRM was 16% (95% CI, 14-18). At 5 y, 11% (95% CI, 10-13) had subsequent malignancies, mostly therapy-related myeloid neoplasms (6%) and non-melanoma skin cancer (3%); none were directly attributed to axi-cel. Conclusions: This real-world study showed sustained survival at 5 y among pts with R/R LBCL treated with axi-cel after ≥2 LOT, consistent with ZUMA-1. Infection and organ failure were common causes of NRM. These results continue to support the use of axi-cel with curative intent in R/R LBCL.

7023 Background: Axi-cel is an autologous chimeric antigen receptor (CAR) T-cell therapy approved for adults with R/R LBCL after ≥ 1 prior line of therapy (LoT). Adverse events, such as cytokine release syndrome (CRS) and neurologic events (NEs), may deter centers from using axi-cel in an outpatient (OPT) setting, though individual centers have observed comparable safety and effectiveness in OPT and inpatient (IPT) care (Furqan et al. Blood Adv . 2024). Here, we present safety and effectiveness outcomes of axi-cel by intention to treat in OPT and IPT settings in a multicenter real-world dataset. Methods: Pts receiving axi-cel for R/R LBCL in the US from 01/2021-07/2023 with data in the Center for International Blood and Marrow Transplant Research (CIBMTR) registry were eligible for analysis. Pts with prior allogeneic transplant or unknown intended care setting were excluded. Of potential pts, 119 OPT pts were identified from 29 centers where an increasing trend was seen (9.6% of pts in 2021 were OPT, 13.5% in 2022, 22.8% in 2023). Pts were matched to 119 IPT pts by propensity score matching on age, sex, comorbidities, lactate dehydrogenase (LDH), bulky disease, prior LoT, chemosensitivity, and infusion year (see table). Results: OPT pts had median age of 63 y (25% ≥ 70), 66% were male, and 67% had ≥ 1 comorbidity. Half (50%) had elevated LDH and 73% had 1 prior LoT. Bulky disease was reported in 3%, and 60% had chemo-resistant disease. Outcomes were analyzed at median follow-up of 12 mo. Safety and effectiveness outcomes were similar between OPT and IPT pts (see table). In multivariate analyses, no differences were found between intended care setting and CRS (odds ratio [OR] 1.09 [95% CI 0.51-2.35]), CRS Gr ≥ 3 (OR 0.57 [0.12-2.60]), NEs (OR 1.14 [0.65-2.00]), or NEs Gr ≥ 3 (OR 0.98 [0.48-2.00]). Among OPT pts, 24% and 50% did not require hospital admission within 30 d and 3 d, respectively. In pts aged ≥ 70 y, only any Gr NEs were higher in the OPT group. Conclusions: After matching on key factors that may be used to select pts for OPT infusion, outcomes were comparable between intended care settings. These findings corroborate prior results and support the consideration of axi-cel in appropriate OPT care settings. Outcomes between matched pts with R/R LBCL receiving axi-cel intended for OPT or IPT. OPT (n=119) a IPT (n=119) a CRS any Gr / Gr ≥ 3 83 (75−89) / 3 (<1−7) 83 (74−89) / 4 (1−10) NE any Gr / Gr ≥ 3 47 (38−57) / 19 (12−27) 46 (37−56) / 21 (14−30) Overall / complete response rates 78 (69−85) / 68 (59−76) 76 (67−83) / 62 (52-70) Duration of response @ 12 mo 64 (52−74) 69 (58−78) Progression-free survival @ 12 mo 53 (43−62) 53 (43−61) Overall survival @ 12 mo 71 (61−78) 72 (62−79) Non-relapse mortality @ 12 mo 6 (2−11) 4 (1−8) Hospital admission within 30 days of infusion / median duration (range), d 76 (67−83) / 9 (2−53) Not Applicable a Percent (95% CI) unless otherwise specified.