Polatuzumab vedotin-containing regimens as bridge to CART: analysis from the CART-SIE study

High tumor burden negatively affects responses to anti-CD19 chimeric antigen receptor T-cell (CART) therapy in large B-cell lymphoma (LBCL). Therefore, bridging therapy (BT) is crucial for disease control before infusion. Here, we retrospectively compared polatuzumab vedotin (PV) combined with rituximab (R)  bendamustine (B) in a cohort of 200 LBCL patients enrolled in the prospective, multicenter, observational CART-SIE study. Commercial CART were infused between July 2020 and January 2025. Patients received BT with either PV-BR (n=122) or PV-R (n=78). At median follow-up of 11.9 months, median progression-free (PFS) and overall survival (OS) in the entire cohort were 10.1 and 35.1 months after CART, respectively. When comparing PV-BR with PV-R treated groups, patient characteristics at CART eligibility, objective response rates to BT (52.5% vs 49.4%, p=0.775), median PFS (13.4 months vs 7.4 months, p=0.556), and median OS (not reached vs 29.0 months, p=0.954) were similar. Hematological toxicities after BT were higher with PV-BR than PV-R (36.4% vs 18.2%, p=0.010; grade≥3 16.1% vs 6.5%, p=0.048), as were rates of neurotoxicity after CART (31.1% vs 15.4%, p=0.019). Rates of cytokine release syndrome and infections were comparable between the two groups. High tumor burden at CART infusion was independent risk factor for both PFS and OS. Our findings confirmed the role of BT and suggested that PV-regimens may effectively control the disease during T-cell manufacturing. Responses and survivals were similar between PV-R and PV-BR, with PV-R showing a trend toward lower toxicity, including reduced neurotoxicity, supporting its potential as a targeted, well-tolerated bridging regimen.