662 | OUTCOMES WITH CAR‐T AND SUBSEQUENT THERAPIES IN PATIENTS WITH T CELL HISTIOCYTE‐RICH LARGE B‐CELL LYMPHOMA, UK EXPERIENCE

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T cell histiocyte rich large B cell lymphoma (THRBCL) is a rare subtype of DLBCL with relatively few tumour B cells and a rich microenvironment of T cells and histiocytes. Some patients develop THRBCL de novo, whilst others have “transformed” disease from nodular lymphocyte predominant Hodgkin lymphoma (NHLPL), considered Fan Pattern E by current WHO criteria. Whilst outcomes for this disease with chemotherapy are similar to DLBCL, the outcomes with newer modalities of treatment are unknown. Many pivotal studies allowed THRBCL patients to enrol, but their numbers were too few to analyse separately. There is real world evidence that patients with THRBCL have inferior outcomes to CAR-T therapy than those with DLCBL. The aim of this study was to analyse outcomes of patients with THRBCL who received CAR-T in the UK and to assess outcomes following progression. We analysed 33 consecutive patients with THRBCL who were approved for treatment with axicabtagene ciloleucel or tisagenlecleucel between December 2018 and November 2024 across UK CAR-T centres. Outcome data is routinely collected on patients undergoing CAR-T therapy and outcomes with subsequent therapies was retrospectively collected. 33 patients from 12 centres were approved for CAR-T therapy of whom 31 received a product. 85% were male and median age at infusion was 47 (IQR 38–57) years. Of the 16 known cases, 31% had a prior diagnosis of NLPHL. Median prior lines of therapy for the high-grade component of disease was 2 (range 1–4). All patients underwent bridging therapy with the majority receiving chemotherapy and 19% receiving radiotherapy. 10% achieved a complete response with bridging and 13% a partial response. None of the 6 patients who had radiotherapy alone achieved a response prior to CAR-T. In infused patients, median PFS is 2.8 months with only 6 patients alive without progression with follow-up ranging between 3 and 35 months post CAR-T, 1 year PFS 17% (95% CI: 5.7–33.5). Median OS is 7.6 months with a 1 year OS of 36.7%. Response to bridging was associated with improved PFS (p = 0.01) and OS (p = 0.031). 4 patients who progressed have since received subsequent bispecific, median OS following progression is 4 months. THRBCL is associated with inferior outcomes to DLBCL with CAR-T, this dataset highlights the need to find alternative therapies for relapsed THRBCL with the majority of patients either refractory or developing early relapses. In contrast to previously reported case series, all patients in this cohort received bridging therapy prior to CAR-T delivery, however outcomes remain significantly inferior when compared to de novo DLBCL either in trials or real world setting with only 17% of patients remaining progression free and alive at 1 year. There are rare cases of long-term responses and therefore until further is known as to potential predictors of response, CAR-T shouldn’t be excluded as a treatment option, especially in those with chemosensitive disease to bridging therapy. Encore Abstract: EHA 2025 Keywords: cellular therapies; aggressive B-cell non-Hodgkin lymphoma Potential sources of conflict of interest: D. El Sharkawi Consultant or advisory role: Abbvie ASTEX AstraZeneca Beigene Janssen Kyowa Kirin Lilly Roche Sobi Honoraria: Abbvie Adaptive AstraZeneca Beigene Gilead Janssen Nurix Roche Takeda Educational grants: Abbvie Novartis Roche F. Seymour Consultant or advisory role: Takeda and Janssen Honoraria: Pfizer, Kite, Janssen A. Hwang Honoraria: Kite Gilead B. Uttenthal Consultant or advisory role: Sartorius, Analog Devices Honoraria: Novartis, Gilead, Atara and Kyverna Educational grants: Kyverna, Novartis, Gilead, Takeda, Jazz, Abbvie A. Kuhnl Consultant or advisory role: Kite/Gilead, Novartis, Abbvie, Sobi, Roche, BMS Honoraria: Kite/Gilead Educational grants: Kite/Gilead, AstraZeneca

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