RADIOTHERAPY BRIDGING IN LARGE B‐CELL LYMPHOMA PATIENTS RECEIVING CD19 CAR‐T – THE UK EXPERIENCE

Abstract

Background: Radiotherapy (RT) has potential synergistic effects with CAR T but is not widely used as bridging therapy for lymphoma patients due to logistical challenges, uncertainty about patient selection and lack of standardised protocols. Published data on RT bridging are so far restricted to single-centre analyses. Methods: We analysed RT bridging in a large multi-centre national cohort of large B-cell lymphoma (LBCL) patients approved for 3rd line axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) between December 2018 and October 2022 across 12 UK centres. Results: Of 763 approved patients, 722 (95%) were leukapheresed, 717 had data available on bridging therapy. 170/717 (24%) received RT bridging, 129 as single modality and 41 as combined modality treatment (CMT). Use of RT bridging varied between centres from 11% to 32%, and increased from 19% (2018–19) to 26% (2021–22; p = 0.034). Median age of RT bridged patients was 60 y. 69% had de novo LBCL, 8% PMBL, 35% tFL and 6% transformed from other low-grade lymphoma. Disease characteristics for RT bridged patients with available data were as follows: 66% advanced stage, 41% bulk, 87% elevated LDH, 42% IPI ≥ 3, 17% double/triple hit. Patients given single modality RT were less likely to have advanced stage or ≥2 extranodal sites versus those receiving systemic therapy/CMT (61% vs. 85/83% and 18% vs. 30/39%, respectively; p < 0.05). Median time from approval to infusion was 56 days with no difference between bridging modalities. Infusion rates were 88% for RT bridging (vs. 84%, 85%, 85% for no bridging, steroids, or systemic therapy, respectively (p = 0.41)). Data on bridging (in-field) response was available for 46 RT patients: 10% CR, 65% PR, 6% SD, 10% PD. Details on RT techniques, anatomical locations and toxicities were available for 68 patients and will be provided at the meeting. Doses of 2–39 Gy were used, including combination of multiple doses; 40 patients received IMRT. Only one patient experienced G3–4 toxicity from RT. The overall incidence of G ≥ 3 CRS was 5.2% and G ≥ 3 ICANS 16.3%, with no significant difference according to bridging approaches. Median follow-up was 16 months. RT bridged patients had favourable outcomes with 1-y PFS of 56% for single modality and 47% for CMT, and 1-y OS of 65% and 56%, respectively (Figure 1). RT bridging was associated with favourable outcomes both in limited and advanced stage (1-y PFS 59% (43—72) and 50% (39–61), respectively. Keywords: aggressive B-cell non-Hodgkin lymphoma, cellular therapies, radiation therapy Conflicts of interests pertinent to the abstract A. Kuhnl Consultant or advisory role: Kite/Gilead, Novartis, BMS Honoraria: Kite/Gilead, Novartis A. Kirkwood Honoraria: Kite/Gilead A. Gibb Consultant or advisory role: Kite/Gilead A. Latif Honoraria: Kite/Gilead, Novartis