BOOM-BOOM RADIATION PRIOR TO LISOCABTAGENE MARALEUCEL IS FEASIBLE AND CONTRIBUTES TO HIGH COMPLETE RESPONSE RATES FOR AGGRESSIVE B-CELL NON-HODGKIN LYMPHOMA

Introduction: Low dose radiation therapy (RT), 4 Gray administered over 2 fractions (BOOM-BOOM), has demonstrated efficacy and low toxicity in B-cell lymphoma. Pre-clinical experiments demonstrate that BOOM-BOOM RT prior to CAR T-cell therapy successfully enhances CAR T-cell efficacy, suggesting engagement of immunotherapeutic mechanisms. We hypothesized that BOOM-BOOM radiation would be safe and effective as bridging therapy prior to liso-cel infusion.

Methods: We performed an investigator-initiated study of BOOM-BOOM bridging RT prior to liso-cel. Eligible patients included adults with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma at the University of Nebraska Medical Center. Subjects received BOOM-BOOM RT to disease sites 7–10 days prior to liso-cel. No other bridging therapy beyond steroids was allowed. The primary endpoint was feasibility, defined as the percentage of subjects enrolled who received BOOM-BOOM RT and liso-cel.

Results: The trial has completed recruitment, and this is the first analysis of feasibility and efficacy for the whole cohort. The median follow-up is 146 days. Thirty-two subjects were enrolled and 30 subjects received BOOM-BOOM RT and liso-cel (30/32, 94%), meeting the prespecified feasibility threshold of > 70%. The median age was 70 (range 23–84), 22 (69%) subjects were male. Three subjects were diagnosed with high-grade B-cell lymphoma, 1 with grey zone lymphoma, 1 with Richter’s transformation, and 27 with DLBCL. Fourteen subjects (18/32, 56%) had a LDH above the upper limit of normal. Twenty-nine subjects (29/32, 91%) received liso-cel as second line therapy. Twenty-one subjects (21/32, 66%) had extranodal disease, 20/32 (63%) were advanced stage, and 16/32 (50%) were refractory to frontline therapy.

Twenty-nine subjects receiving per-protocol therapy were evaluable for response using Lugano criteria for PET/CT. Responses to BOOM-BOOM and liso-cel were observed in 25/29 (86%) subjects, and the complete response (CR) rate was 24/29 (83%). Two subjects had stable disease, and 2 subjects experienced progressive disease as best response. Progression-free survival (PFS) and overall survival (OS) curves are depicted in Figure 1. A landmark analysis by response at D30 for PFS and OS is depicted in Figure 1C/D and demonstrates a 200-day PFS and OS rate for patients obtaining a CR of 75% (95% CI: 46%–90%) and 89% (95% CI: 62%–97%), respectively.

Thirty subjects were evaluable for safety. CRS was observed in 15 subjects and was G1–2 in 14 and G5 in one. Immune effector cell-associated neurotoxicity was observed in 8 subjects and G3–4 in 5/8. Two subjects died, 1 due to intestinal perforation and 1 due to septic shock prior to D100.

Conclusion: The combination of BOOM-BOOM RT and liso-cel met our primary endpoint of feasibility and produced a high CR rate of 83%. These data suggest that the use of low-dose RT as bridging therapy is safe, feasible, and may be effective at enhancing outcomes to liso-cel therapy.

Research funding declaration: Bristol Myers Squibb

Encore Abstract: EHA 2025

Keywords: cellular therapies; aggressive B-cell non-Hodgkin lymphoma; radiation therapy

Potential sources of conflict of interest:

C. D'Angelo

Employment or leadership position: N/A

Consultant or advisory role: Beigene, ADC Therapeutics, Abbvie, Genmab, Bristol Myers Squibb

Stock ownership: N/A

Honoraria: N/A

Educational grants: N/A

Other remuneration: N/A

J. Vose

Consultant or advisory role: Genmab, Abbvie

Honoraria: Novartis

M. Lunning

Consultant or advisory role: Genmab, Abbvie, Bristol Myers Squibb