1120 - Salvage Radiotherapy in LBCL After First Line Chemo-immunotherapy: Can We Avoid CAR-T Therapy?

J. L. Brady¹, R. Begum¹, M. Patel², B. Leung³, and G. Mikhaeel⁴; ¹Guys and St Thomas NHS Foundation Trust, London, United Kingdom, ²Department of Clinical Oncology, Guy´s Cancer Centre, Guy´s and St Thomas´ Hospital, London, United Kingdom, London, United Kingdom, ³Guys and St Thomas NHS foundation trust, London, United Kingdom, ⁴School of Cancer and Pharmaceutical Sciences, Kings College London, London, United Kingdom

Purpose/Objective(s): Persistent metabolic uptake on PET/CT after first line chemotherapy (CT) for Large B cell lymphoma (LBCL) is associated with a poor prognosis. The fit patient (pt) will be considered for CAR-T therapy if refractory disease confirmed, but this is not without the risk of significant toxicity, both short and long term. For pts with localised refractory disease radiotherapy (RT) is an alternative salvage option and may spare some the need for CAR-T or other intensive systemic treatment. In this study we evaluate the outcome of pts receiving RT when not in complete metabolic response (CMR) and look at factors predicting response. Materials/

Methods: This was a retrospective review of LBCL pts with residual FDG uptake on PET/CT after first line CT who received RT at our institution. Eligibility criteria included: treatment with curative intent, R-CHOP CT or similar, post CT PET/CT Deauville score (DS) 4 or 5, RT =30Gy within 8 weeks of CT. End points included: relapse rate, pattern of relapse, response to RT, PFS and OS.

Results: We identified 86 pts who received RT between Mar 2011 and Oct 2023. Pt and treatment characteristics are shown in table 1 below. 62 pts (72.1%) had DS4 and 24 (27.9%) DS5 pre RT. With a median FU of 42.4 months (1.1-164.1) from RT, 26/86 pts (30.2%) have relapsed. Relapses occurred early, at median 3.0 months (0.4-58.1) from RT. 3/26 (11.5%) relapses were in field, 17/26 (65.4%) out field and 6/26 (23.1%) in both. 11/24 (45.8%) pts with DS5 pre RT have relapsed compared to 15/62 (24.2%) with DS4. Relapses were less common in stage I/II disease, 7/42 pts (16.7%) vs 19/44 (43.2%) in advanced stage disease. There was no association between RT dose and relapse rate. 79 (91.9%) pts had a PET/CT after RT. 45/79 (57%) achieved CMR, 15 (19.0%) DS4 and 19 (24.1%) DS5 .17/19 (89.5%) pts with DS5 post RT progressed vs 1 /15 (6.7%) with DS4 and 4/45 (8.9%) with CMR DS1-3. Median PFS and OS were not reached. Estimated 2 year PFS and OS were 72.9% and 80.2%, and 5 year PFS and OS, 64.2% and 74.8% for the whole cohort. For pts with DS4 pre RT, outcomes were excellent with 2 year PFS and OS of 82% and 84.7%, vs 49% and 68.1% in pts with DS5 pre RT.

Conclusion: RT is an effective salvage treatment for many pts with LBCL not in CMR following initial CT and may avoid the need for further intensive systemic treatment including CAR-T. Outcomes were particularly good for patients with DS4 post CT, with the majority of this group achieving durable remissions after RT. Table 1 Patient and treatment Characteristics

Male Female	48 (55.8%) 38 (44.2%)
Median age years (range)	62 (20-89)
Histopathology Germinal centre (GC) Non GC PMBCL T-CELL RICH NOS	33 (38.4%) 22 (25.6%) 16 (18.6%) 3 (3.5%) 12 (14.0%)
Stage 1 2 3 4	9 (10.5%) 33 (38.4%) 13 (15.1%) 31 (36.0%)
IPI 0-1 2 3 4-5	32 (37.2%) 21 (24.4%) 14 (16.3%) 19 (22.1%)
Median no CT cycles CT regimen R MiniCHOP R-CHOP/ R Pola CHP R-CVP/RGCVP LMB/R-CODOX-M	6 (3-8) 9 (10.5%) 68 (79.1%) 7 (8.1%) 2 (2.3%)
End of CT DS 4 5	62 (72.1%) 24 (27.9%)
RT dose (Gy) 30/30.6 36 40	29 (33.7%) 40 (46.5%) 17 (19.8%)