Bridging Therapy Before Brexucabtagene Autoleucel in MCL: A Comparison
A study of 176 patients with mantle cell lymphoma (MCL) in the United Kingdom has revealed variations in the use of bridging therapy – treatment administered before receiving brexucabtagene autoleucel (brexu-cel) – and its impact on treatment outcomes, according to research published March 8, 2026, in the British Journal of Haematology.
Researchers found that 90% of patients (158 of 176) received bridging therapy prior to infusion with brexu-cel. The most common approaches involved standard chemotherapy, potentially combined with radiotherapy (53%), or targeted therapy alone (23%). Clinicians tended to favor chemotherapy plus radiotherapy for patients with a higher Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 1, those exhibiting blastoid disease characteristics, those with tumors larger than 5 cm, and those with elevated lactate dehydrogenase levels.
The overall response rate (ORR) among all patients was 46%. Patients receiving standard chemotherapy plus radiotherapy demonstrated a higher ORR of 58%, with the R-BAC regimen achieving a 64% response rate. However, disease progression despite bridging therapy was associated with a significantly lower ORR to brexu-cel (77% versus 91%, p = 0.03) and an increased risk of grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS) (odds ratio 3.43, 95% confidence interval 1.44-8.10, p = 0.01).
The study also highlighted potential drawbacks to different bridging strategies. Standard chemotherapy plus radiotherapy was linked to a higher incidence of grade 3 or higher neutropenia (in month 1), thrombocytopenia (in months 1 and 3), and early non-relapse mortality (13% versus 0% compared to targeted therapy alone). The researchers noted that neither the specific bridging therapy modality used nor the patient’s response to it significantly affected progression-free or overall survival following brexu-cel infusion.
The findings underscore the demand for careful consideration of a patient’s overall health and disease characteristics when selecting a bridging therapy regimen. The authors recommend prioritizing a review of a patient’s hematopoietic reserve before choosing a bridging strategy, along with rigorous management of delayed cytopenia after infusion, and the development of more effective and tolerable bridging therapies. Brexucabtagene autoleucel is a CAR T-cell therapy approved for the treatment of relapsed or refractory MCL, as indicated by clinical trial NCT06553872.
Research published in November 2025 indicated that brexu-cel has been used to treat MCL patients from 2020 to 2025, with bridging therapy, performance status, and elevated LDH levels being factors considered prior to lymphodepletion.