Polatuzumabvedotin (PV) is an antibody-drug conjugate targeting CD79b that is approved for patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). Patients who relapse after CAR T-cell therapy were not included in the registration study, and reports of PV use after CAR T-cells are limited. This is a multi-center retrospective analysis of patients with LBCL who relapsed or progressed after CAR T-cell therapy and subsequently received PV with or without rituximab and bendamustine, between 07/2019 and 05/2021. Response to treatment and progression were assessed based on 2014 Lugano criteria. Fifty-seven patients were included in the study: 18 (32%) patients were primary refractory to CAR T-cell therapy, and 34 (60%) patients received PV-based therapy immediately after CAR T cell therapy. PV was combined with rituximab in 54 (95%) patients and administered with bendamustine in 35 (61%). A response was achieved in 25 (44%) patients, including complete remission in 8 (14%) patients. No significant association between baseline characteristics and response was observed. After a median follow up of 47 weeks (95% confidence interval [CI], 40-54 weeks), 46 (81%) patients had progressed or died, and the median PFS was 10 weeks (95% CI, 5-15 weeks). On a multivariate analysis, bone marrow involvement (hazard ratio [HR] 5.2; 95% CI 1.8-15, p=0.003) and elevated LDH (HR 5.0; 95% CI 1.4-16, p=0.01)were associated with shorter PFS. Studies aimed at better characterizing intrinsic mechanism of resistance and to identify optimal consolidation strategies for these patients are warranted.