Outcomes of Bridging Therapy in Patients With Relapsed/Refractory Large B Cell Lymphoma Receiving Third-Line CAR T

Bridging therapy (BT) is frequently used in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) undergoing chimeric antigen receptor T cell (CAR T) therapy, but the optimal BT approach remains uncertain. We evaluated BT strategies and their associations with response and survival outcomes. Accordingly, we included patients with R/R LBCL evaluated for third-line or later CD19-directed CAR T at Princess Margaret Cancer Center from 2017 to 2024 (follow-up to 01/2025). BT modalities included chemotherapy, polatuzumab-based chemotherapy, radiotherapy, corticosteroids, and none. We assessed the associations of BT modality with overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) using logistic regression and Cox models. Among 219 patients, 188 underwent apheresis and 157 (84%) received CAR T. Of those apheresed, 79% received BT (radiotherapy 41%, polatuzumab-based 26%, third-line chemotherapy 16%, corticosteroids 17%, while 21% received no BT). ORR was highest with polatuzumab (50%) and radiotherapy (40%) versus chemotherapy (16%) (p = 0.009). Median ΔSUVmax in 84 patients was higher in polatuzumab and radiotherapy treated patients, compared to chemotherapy (p < 0.001). Radiotherapy encompassing all active disease had higher ORR (51%) versus non-comprehensive (12%) (p = 0.04). Two-year PFS was highest with radiotherapy (47%) and polatuzumab (37%) BT versus chemotherapy (21%). Adjusted analyses showed improved PFS with radiotherapy (adjusted hazard ratio [aHR] 0.29) and polatuzumab (aHR 0.41). OS was also improved with radiotherapy (HR 0.40). Chemotherapy BT was associated with the highest 2-year lymphoma-related mortality (74%). In conclusion, polatuzumab-based and radiotherapy BT as well as no BT were associated with improved responses and outcomes compared to chemotherapy. Although these results may have been influenced by patient selection, prospective studies integrating these approaches are needed to define optimal, individualized BT strategies.