Bridging Radiotherapy Shows Promise in Reducing CAR-T Cell Therapy Toxicity Across B-Cell Lymphoma and Multiple Myeloma
Key Insights
Bridging radiotherapy (search) before CAR-T cell therapy (search) significantly reduced severe treatment-related toxicities, with only 5% of B-cell lymphoma (search) patients experiencing grade 3 or higher cytokine release syndrome (search).
In multiple myeloma (search) patients, bridging radiotherapy (search) demonstrated excellent safety with no grade 3 or higher toxicities observed and improved progression-free survival outcomes.
Elevated lactate dehydrogenase (search) levels after bridging radiotherapy (search) were associated with higher toxicity, while normalized LDH levels correlated with significantly fewer severe events.
Bridging radiotherapy (search) administered before CAR-T cell therapy (search) appears to reduce severe treatment-related toxicities while maintaining therapeutic efficacy, according to new research presented at major oncology conferences. The findings from two separate studies suggest this approach could improve the safety profile of CAR-T therapy across different hematologic malignancies.
Significant Toxicity Reduction in B-Cell Lymphoma
A comprehensive analysis of 116 B-cell lymphoma (search) patients who received bridging radiotherapy (search) prior to CAR-T therapy between 2016 and 2024 revealed substantially lower rates of severe complications. The study, presented at the 2025 International Conference on Malignant Lymphoma, found that cytokine release syndrome (search) occurred in 74% of patients, but severe grade 3 or higher CRS was observed in only 5% of cases.
Immune effector cell-associated neurotoxicity syndrome (search) was reported in 25% of patients, with 12% experiencing grade 3 or higher severity. These rates represent a notable improvement over historical CAR-T toxicity profiles, suggesting that bridging radiotherapy (search) may provide protective benefits through disease cytoreduction.
The analysis revealed important differences between CAR-T products, with patients treated with axicabtagene (search) showing higher rates of CRS of any grade at 91% (p=0.001). However, no specific CAR-T product was associated with increased rates of severe toxicity. The concurrent use of systemic therapy alongside bridging radiotherapy (search) did not increase the risk of high-grade CRS or ICANS.
Biomarker-Guided Approach Shows Promise
A key finding from the lymphoma study identified lactate dehydrogenase (search) levels as a potential biomarker for toxicity prediction. Elevated LDH levels after bridging radiotherapy (search) were associated with higher toxicity rates, while patients whose LDH normalized following treatment experienced significantly fewer severe events.
The delivery of higher biological effective doses of radiation was linked to greater LDH reduction and lower overall toxicity. These findings suggest that LDH levels and biological effective dose may serve as useful tools for guiding bridging strategies and early toxicity risk assessment.
Multiple Myeloma Results Demonstrate Safety
Parallel research in relapsed/refractory multiple myeloma (search) provided additional evidence for the safety of bridging radiotherapy (search). A retrospective analysis of 19 patients who received bridging radiotherapy prior to anti-BCMA CAR-T cell therapy showed no grade 3 or higher toxicities related to the bridging treatment.
The multiple myeloma (search) study, presented at the 2025 American Society of Radiation Oncology Annual Meeting, reported that only 2 patients experienced grade 2 cytokine release syndrome (search) and 2 developed grade 2 ICANS, with no grade 3 events observed for either complication.
Efficacy Outcomes Support Treatment Approach
Beyond safety benefits, the bridging radiotherapy (search) approach demonstrated encouraging efficacy signals. In the multiple myeloma (search) cohort, the median progression-free survival was 6.8 months after a median follow-up of 8.2 months, with median overall survival not yet reached.
Patients without extramedullary disease (search) showed statistically significant improvement in progression-free survival, with a median PFS of 10.4 months compared to 6.6 months among patients with extramedullary disease (P = 0.006). Among patients with extramedullary disease, those receiving comprehensive bridging radiotherapy (search) showed a trend toward improved PFS compared to focal treatment, with median PFS of 6.7 months versus 4.4 months (P = 0.055).
Treatment Protocols and Future Directions
The most commonly used radiation protocols in the multiple myeloma (search) study included 20 Gy delivered in 5 fractions for 6 patients and 8 Gy in a single fraction for 8 patients. Comprehensive bridging radiotherapy (search), which encompassed radiation to all sites of extramedullary disease (search), appeared to offer superior outcomes compared to focal approaches.
A phase 2 single-arm trial is currently ongoing to further evaluate comprehensive bridging therapy for multiple myeloma (search) patients with extramedullary disease (search) prior to CAR-T cell therapy (search). The trial has enrolled 26 patients, all receiving bridging therapy to all sites of extramedullary disease, with a primary endpoint of improving 12-month progression-free survival from 25% to 50%.