Dr Wang on the Role of Bridging Radiotherapy Prior to CAR T-Cell Therapy in B-Cell Lymphoma

“CNS disease is hard to control [with CAR T-cell therapy] due to the blood-brain barrier, tumor microenvironment, and risks [such as] ICANS. That’s where bridging radiotherapy comes in. By using radiation before CAR T, we can provide cytoreduction address bulky disease, address symptomatic disease, reduce [disease] relapse risk, and potentially improve CAR T efficacy.”

Pule Wang, MD, a radiation oncology resident in the Department of Radiation Oncology at City of Hope, discussed the role of central nervous system (CNS) bridging radiotherapy prior to CAR T-cell therapy for the treatment of patients with B-cell lymphomas.

CAR T-cell therapy has produced transformative outcomes for the treatment of patients with relapsed/refractory B-cell lymphoma, Wang began. The approach has displayed successful CNS trafficking; however, a remaining clinical challenge lies in the fact that CNS disease is difficult to control, she continued. This is due to factors including the blood-brain barrier, a complex tumor microenvironment, and risks of adverse effects such as immune effector cell-associated neurotoxicity syndrome, she explained.

To address some of these unmet needs, bridging radiation therapy is used before the administration of CAR T-cell therapy, Wang said. This approach can lead to cytoreduction, address bulky and symptomatic disease, reduce the risk of disease relapse, and potentially improve the efficacy of CAR T-cell therapy, she noted. Bridging radiotherapy can also be tailored to the needs of an individual patient via techniques such as partial brain radiation in order to minimize potential toxicities in the setting of limited disease, she concluded.

During the 2025 American Society for Radiation Oncology (ASTRO) Annual Meeting, Pule presented findings from a retrospective study which examined the role of bridging radiation therapy prior to CAR T-cell therapy in patients with CNS involvement from relapsed/refractory B-cell lymphomas. The study included 26 patients treated at City of Hope from June 2019 to January 2025.