A Prospective Clinical Trial of Boom-Boom Radiation As Bridging Therapy for Patients with Large B-Cell Lymphoma Undergoing Treatment with Lisocabtagene Maraleucel (Liso-cel) Therapy

• Published in: Blood 2024-11, Vol.144, p.3126-3126
• Main Authors: D'Angelo, Christopher R, Enke, Charles, Vose, Julie M., Bociek, Robert Gregory, Yu, Fang, Schissel, Makayla, Lunning, Matthew
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-208472

Introduction: Many patients receiving chimeric antigen receptor T-cell (CAR T)-cell therapy for aggressive B-cell non-Hodgkin lymphoma will fail to respond or relapse. Bridging therapy, administered between pheresis and infusion, is used to control disease prior to CAR T-cell infusion. The impact of bridging therapy has been difficult to determine as majority of data is retrospective with bridging therapy heterogeneously employed. Low dose radiation, 2 Gray administered in 2 fractions (Boom-Boom), has demonstrated efficacy and exceptionally low toxicity in palliation of localized B-cell lymphoma. Pre-clinical experiments have demonstrated that Boom-Boom radiation administered prior to CAR T-cell therapy successfully enhances CAR T cell efficacy, suggesting potential engagement of novel 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, pilot feasibility study of Boom-Boom bridging radiation therapy prior to liso-cel infusion. Eligible patients included adults aged 19+ with a diagnosis of aggressive B-cell non-Hodgkin lymphoma eligible to receive liso-cel under commercial indication at the University of Nebraska Medical Center. Subjects received Boom-Boom (2 x 2 Gy) radiation to disease sites approximately 7-10 days prior to liso-cel infusion. No other bridging therapy aside from steroids was allowed after lymphocyte pheresis. The primary endpoint was feasibility, defined as the percentage of subjects receiving boom-boom radiation that go on to receive CAR T-cell infusion. Based on prior clinical trial data for TRANSCEND and TRANSFORM, we set a feasibility threshold at 70% for enrolled subjects to receive boom-boom and CAR T-cell therapy. Results: The trial is ongoing and this data represents an interim analysis. Twenty subjects enrolled and underwent lymphocyte pheresis. Eighteen subjects received Boom-Boom radiation and liso-cel infusion, with 2 subjects removed for advanced disease requiring alternative therapy. The study is meeting prespecified feasibility criteria with 18/18 (100%) subjects who received Boom-Boom proceeded to liso-cel infusion, and 18/20 (90%) subjects enrolled and intended for liso-cel received Boom-Boom and liso-cel. The median age was 70 (range 23-84), 13 (65%) subjects were male, 100% were Caucasian and 1 subject (5%) was Hispanic. The median distance for subjects to our center was 93 mile