Pule Wang, MD, is a radiation oncology resident in the Department of Radiation Oncology at City of Hope in Duarte, California.

Dr Wang on the Safety Profile of CNS Bridging Radiotherapy Prior to CAR T in B-Cell Lymphoma

“The safety profile that we observed was very acceptable. We did not observe any grade 2 or higher acute or late radiation-related neurotoxicity.”

Pule Wang, MD, a radiation oncology fellow in the Department of Radiation Oncology at City of Hope, discussed safety data from a retrospective study of bridging radiation therapy prior to CAR T-cell therapy in patients with central nervous system (CNS) involvement from relapsed/refractory B-cell lymphomas.

The study included 26 patients with relapsed/refractory B-cell lymphoma involving the CNS who were treated with bridging radiation therapy followed by CAR T-cell therapy at City of Hope; the patient population consisted of those with diffuse large B-cell lymphoma (n = 22) and mantle cell lymphoma (n = 4). During the 

2025 American Society for Radiation Oncology (ASTRO) Annual Meeting

, Wang presented findings from the study which showed that patients who received partial brain radiation (n = 18), who had a median gross tumor volume of 19.38 cc (range, 4.42-51.02), experienced a mean decrease of lesion size prior to CAR T-cell therapy of 43.0% (95% CI, 22.2%-63.8%).

In terms of safety, the profile of the treatment approach was acceptable, Wang began. There were no instances of grade 2 or higher acute or late onset bridging radiation therapy neurotoxicity among patients with brain parenchymal disease (n = 14), she noted. A significant portion of this subgroup (35.7%) received memantine for neuroprotection, she noted.

Following CAR T-cell therapy 10 patients in the overall population (n = 26) immune effector cell-associated neurotoxicity syndrome (ICANS), Wang said. This rate is similar to that reported in the historical literature of CAR T-cell therapy, she added. 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, she noted. Overall, the toxicity profile of the approach examined in the retrospective study was similar with that of patients who received CAR T-cell therapy alone, she concluded.

Videos

Pule Wang, MD, discusses safety data with CNS bridging radiotherapy before CAR T in B-cell lymphoma.

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

“Patients who received partial brain radiation had good outcomes. We demonstrated that whole brain radiation is not needed for those patients with 1 to 2 lesions.”

Pule Wang, MD, a radiation oncology fellow in the Department of Radiation Oncology at City of Hope, discussed the key efficacy findings from a retrospective study which evaluated the role of bridging radiation therapy prior to CAR T-cell therapy in patients with central nervous system (CNS) involvement from relapsed/refractory B-cell lymphomas.

The study included 26 patients with relapsed/refractory B-cell lymphoma involving the CNS who were treated with bridging radiation therapy followed by CAR T-cell therapy at City of Hope. It included patients with diffuse large B-cell lymphoma (n = 22) and mantle cell lymphoma (n = 4). All patients had secondary CNS lymphoma and received brain radiation therapy to a median total dose of 25 Gy (range, 4.0-37.5) in 8 fractions (range, 1-15).

Findings from the study, which were presented by Wang during the 

demonstrated that patients who received partial brain radiation (n = 18) achieved good efficacy outcomes, indicating that whole brain radiation is not needed for patients with a maximum of 1 to lesions, she explained. Patients who received partial brain radiation had a median gross tumor volume of 19.38 cc (range, 4.42-51.02) and achieved a mean decrease of lesion size prior to CAR T-cell therapy of 43.0% (95% CI, 22.2%-63.8%). 

Moreover, patients with brain parenchymal disease (n = 14) experienced a markedly better median overall survival with partial brain radiation compared with those who received whole brain radiation, Wang noted. These findings suggest that in select patients with parenchymal disease, partial brain radiation as bridging therapy to CAR T-cell therapy can provide durable CNS disease control and spare patients from the long-term cognitive risks that are associated with whole-brain treatment, she concluded.

Pule Wang, MD, discusses findings from a retrospective study of CNS bridging radiation therapy prior to CAR T-cell therapy in B-cell lymphomas.

Dr Wang on a Retrospective Study of CNS Bridging Radiotherapy Prior to CAR T in B-Cell Lymphoma

“This was a retrospective study which included 26 patients with relapsed/refractory B-cell lymphoma involving the central nervous system who received bridging radiation [therapy] followed by CAR T at City of Hope.”

Pule Wang, MD, a radiation oncology fellow in the Department of Radiation Oncology at City of Hope, discussed the design of a retrospective study which examined the role of bridging radiation therapy prior to CAR T-cell therapy in patients with central nervous system (CNS) involvement from relapsed/refractory B-cell lymphomas.

The study, findings from which were presented by Wang during the 

 included 26 patients with relapsed/refractory B-cell lymphoma involving the CNS who were treated with bridging radiation therapy followed by CAR T-cell therapy at City of Hope, she began. The median patient age was 66 years (range, 39-81) and the median Karnofsky Performance Status was 80 (range, 40-90), she continued. All of the enrolled patients had secondary CNS lymphoma. Specifically, disease histologies consisted of diffuse large B-cell lymphoma (n = 22) and mantle cell lymphoma (n = 4), she added. 

Wang and her coauthors performed a subgroup analysis of patients with brain parenchymal disease (n=14), since this was the most relevant group to the question of whether to use focal or whole-brain retreatment, she said. Eight patients underwent whole brain radiation and 6 patients received involved site partial brain radiation, she added. Patients also received involved site orbits (n = 3) and involved spine (n = 9) radiation.

The study included patients with neuroaxis disease involving the brain, spinal cord, or leptomeninges. CNS responses were assessed following bridging radiation therapy and after CAR T-cell therapy via International PCNSL Collaborative Group guidelines. The study authors evaluated efficacy outcomes, neurotoxicity and overall survival (OS). OS was elucidated from the end of bridging radiation therapy using Kaplan-Meier curves.

Pule Wang, MD, discusses the design of a retrospective study of CNS bridging radiation therapy prior to CAR T in B-cell lymphomas.

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.

, 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.

Pule Wang, MD, discusses CNS bridging radiotherapy prior to CAR T-cell therapy in B-cell lymphomas.

Pule Wang, MD

Articles

Dr Wang on the Safety Profile of CNS Bridging Radiotherapy Prior to CAR T in B-Cell Lymphoma

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

Dr Wang on a Retrospective Study of CNS Bridging Radiotherapy Prior to CAR T in B-Cell Lymphoma

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