Background: Anti-CD19 chimeric antigen receptor modified T-cell therapies (CAR-T) have expanded the treatment possibilities for many patients with relapsed/refractory (R/R) aggressive large B-cell lymphomas (B-NHL) but fails to achieve remissions in a considerable proportion of patients. In this study, we examined whether response to systemic therapy prior to CAR T-cell infusion is associated with outcome.Methods: We analyzed a retrospective dataset of R/R B-NHL patients (pts) treated with commercially available CAR-T at the University of Pennsylvania treated from April 2018 to August 2020. 18F-FDG PET/CT scans obtained directly prior to and after CAR-T therapy were re-evaluated for response by an independent radiologist using the Lugano 2014 criteria. Association between pre-therapy and post-therapy responses were examined using Fisher’s exact test. Results: 50 pts with aggressive R/R B-NHL were enrolled. 34 pts received tisagenlecleucel and 16 received axi-cel. Median age was 61 (range 29-82), and 27 pts (54%) were men. Most pts (n = 48, 96%) had ECOG performance status of 0-1, with a median number of 3 prior therapies (range 1-11). 14 (28%) of pts had LDH elevation at time of CAR T cell infusion. Median time from pre-therapy PET/CT to infusion was 47 days (range: 6-155). Median PFS was 3.4 months. Prior to CAR T cell infusion, responses were as follows: 12 complete response (CR), 9 partial response (PR), 8 stable disease (SD) and 21 progressive disease (PD). Post-therapy responses were: 20 CR, 5 PR, 2 SD, and 23 PD. 67% of pts with a CR pre-therapy had continued CR after CAR T-cell infusion, whereas 32% pf pts without a CR had a CR after infusion (p < 0.05). There was a trend toward CR/PR immediately prior to CAR T cell infusion being significantly associated with CR after CAR-T. We found that high metabolic tumor volume ( > 350cc vs ≤350cc) was associated with poorer PFS (log rank, p = 0.05). We did not find elevated LDH or use of bridging therapy to be associated with response to CAR-T. Conclusions: This is the largest report of lymphoma patients treated with CAR-T while in remission to date and suggests the importance of optimizing clinical response prior to CAR-T. Although patients in CR were excluded from the registrational trials, it is notable that patients in CR prior to CAR-T had a high rate of CR post CAR T cells despite the absence of active lymphoma on imaging. Longer follow-up is needed to confirm these early observations.