Bridging practices prior to brexucabtagene autoleucel for mantle cell lymphoma in the United Kingdom: An analysis of modality, response, toxicity and survival

Bridging therapy (BT) prior to brexucabtagene autoleucel (brexu-cel) in mantle cell lymphoma (MCL) is supported by limited evidence. Here, we report BT modality and outcome in 176 patients at 15 centres in the United Kingdom. BT was delivered to 90% (158/176), the majority receiving standard chemotherapy +/- radiotherapy (53%) (SD chemo +/- RT) or targeted therapy (TT) alone (23%). Clinicians favoured SD chemo +/- RT in those with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 1, blastoid disease, bulk >5 cm and elevated lactate dehydrogenase. Overall response rate (ORR) was 46%. Higher ORR was observed with SD chemo +/- RT (58%), particularly R-BAC (64%). Progressive disease despite BT was associated with a lower ORR to brexu-cel (77% vs. 91%, p = 0.03) and a higher risk of ≥grade 3 ICANS (OR 3.43, 95% CI 1.44-8.10, p = 0.01). SD chemo +/- RT was associated with a higher incidence of ≥grade 3 neutropenia (Month 1), ≥grade 3 thrombocytopenia (Month 1, Month 3) and early non-relapse mortality (<90 days, 13% vs. 0%) compared to TT alone. Neither BT modality nor response impacted progression-free or overall survival post-infusion. Review of haematopoietic reserve prior to the selection of BT regimen, rigorous management of delayed cytopenia post-infusion and more effective and tolerable BT should be prioritised.