CNS Bridging Radiotherapy Shows Acceptable Safety Profile Prior to CAR-T in B-Cell Lymphoma
核心洞察
A retrospective study of 26 patients with relapsed/refractory B-cell lymphoma (搜索) involving the central nervous system demonstrated that bridging radiation therapy (搜索) prior to CAR-T cell therapy (搜索) has an acceptable safety profile.
Patients who received partial brain radiation experienced a mean decrease of lesion size of 43.0% prior to CAR-T therapy, with no grade 2 or higher acute or late radiation-related neurotoxicity observed.
The rate of immune effector cell-associated neurotoxicity syndrome (搜索) (ICANS) following CAR-T therapy was 38.5%, similar to historical literature rates for CAR-T therapy alone.
A retrospective study from City of Hope (搜索) has demonstrated that bridging radiation therapy (搜索) prior to CAR-T cell therapy (搜索) shows an acceptable safety profile in patients with relapsed/refractory B-cell lymphoma (搜索) involving the central nervous system (CNS). The findings, presented at the 2025 American Society for Radiation Oncology (搜索) (ASTRO) Annual Meeting, provide important insights into managing CNS involvement in this challenging patient population.
Study Design and Patient Population
The study included 26 patients with relapsed/refractory B-cell lymphoma (搜索) involving the CNS who received bridging radiation therapy (搜索) followed by CAR-T cell therapy (搜索) at City of Hope (搜索). The median patient age was 66 years (range, 39-81) and the median Karnofsky Performance Status was 80 (range, 40-90). All enrolled patients had secondary CNS lymphoma, with disease histologies consisting of diffuse large B-cell lymphoma (搜索) (n = 22) and mantle cell lymphoma (搜索) (n = 4).
The study population included patients with neuroaxis disease involving the brain, spinal cord, or leptomeninges. Researchers performed a subgroup analysis of patients with brain parenchymal disease (n=14), as this was the most relevant group for determining whether to use focal or whole-brain treatment approaches.
Treatment Approaches and Efficacy
Among the 14 patients with brain parenchymal disease, eight patients underwent whole brain radiation and six patients received involved site partial brain radiation. Additional patients received involved site orbits (n = 3) and involved spine (n = 9) radiation.
Patients who received partial brain radiation (n = 18) had a median gross tumor volume of 19.38 cc (range, 4.42-51.02) and experienced a mean decrease of lesion size prior to CAR-T cell therapy (搜索) of 43.0% (95% CI, 22.2%-63.8%). CNS responses were assessed following bridging radiation therapy (搜索) and after CAR-T cell therapy using International PCNSL Collaborative Group guidelines.
Safety Profile and Neurotoxicity
The safety profile observed in the study was notably acceptable. Researchers found no instances of grade 2 or higher acute or late onset bridging radiation therapy (搜索) neurotoxicity among patients with brain parenchymal disease. A significant portion of this subgroup (35.7%) received memantine for neuroprotection.
Following CAR-T cell therapy (搜索), 10 patients in the overall population (38.5%) developed immune effector cell-associated neurotoxicity syndrome (搜索) (ICANS). This rate is similar to that reported in the historical literature of CAR-T cell therapy. In the subgroup of patients with brain parenchymal disease, the rate of ICANS was slightly higher with partial brain radiation compared with whole brain radiation.
Clinical Implications
According to Dr. Pule Wang, a radiation oncology fellow in the Department of Radiation Oncology at City of Hope (搜索) who presented the findings, the toxicity profile of the bridging radiation therapy (搜索) approach was similar to that of patients who received CAR-T cell therapy (搜索) alone. This suggests that the addition of bridging radiation therapy does not significantly increase the overall toxicity burden for patients.
The study evaluated efficacy outcomes, neurotoxicity, and overall survival, with overall survival calculated from the end of bridging radiation therapy (搜索) using Kaplan-Meier curves. The research provides valuable data for clinicians considering treatment strategies for patients with CNS involvement from relapsed/refractory B-cell lymphomas, a particularly challenging clinical scenario.