Introduction: Tafasitamab (tafa) is a CD19-targeting immunotherapy indicated in combination with lenalidomide (len) for the treatment of adult patients with R/R DLBCL ineligible for autologous stem cell transplantation (ASCT). The 2020 FDA accelerated approval of tafa in this setting was based on findings from L-MIND, a multicenter, open-label, single-arm, phase 2 trial (Salles G, et al. Lancet Oncol. 2020;21:978-988). Since this approval, there has been a paucity of real-world studies (RWS) evaluating the outcomes of patients with R/R DLBCL who received tafa in the community setting. We conducted this RWS to describe the patient characteristics, treatment patterns, and outcomes of patients who received tafa for R/R DLBCL across practice settings in the US. Methods: A retrospective, multisite, physician-abstracted medical chart review RWS was conducted in US adults who initiated tafa (with or without len) on or after Oct 21, 2020 for R/R DLBCL outside of the clinical trial setting. Patients were required to have at least 4 months of follow-up after tafa initiation unless the patient died during this period. Participating physicians from Cardinal Health's Oncology Provider Extended Network-approximately 83% from community oncology practices-abstracted data from the medical records of patients into electronic case report forms. Data were summarized using descriptive statistics for all patients and for subgroups based on whether tafa was received as second-line (2L) or third-line (3L) therapy for R/R DLBCL. Whereas some patients received tafa as fourth-line (4L) or fifth-line (5L) therapy, data for these patients were not analyzed separately due to small numbers. Results: A total of 181 patients were included in this study, with a median follow-up time of 6.5 (range, 0.9-27.4) months since initiating tafa. Key patient characteristics, treatment patterns, and outcomes are summarized in Table 1. At initiation with tafa, the majority of patients had an Eastern Cooperative Oncology Group performance status of 0-2 (98%), Ann Arbor stage of III-IV (93%), and a revised International Prognostic Index score of 3-5 (75%). The majority of patients (72%) received tafa as 2L therapy for R/R DLBCL, whereas 24% received tafa as 3L, 3% as 4L, and 2% as 5L. The median time from initial diagnosis of DLBCL to initiation of tafa was 20 (interquartile range [IQR], 12-35) months. Prior to tafa, 12% had undergone ASCT and 3% had received chimeric antigen receptor T-cell therapy. The starting dose of concomitantly administered len varied: 68 (38%) received 25 mg; 43 (24%) received 20 mg; 29 (16%) received 15 mg; 31 (17%) received 10 mg; 2 (1%) received 5 mg; and 8 (4%) patients did not receive concomitant len. Len dose reductions were experienced during treatment by 19% of patients. Among the 60 patients who discontinued tafa, reasons for discontinuation included progression confirmed by scan (50%), progression defined clinically (17%), toxicity (15%), patient/caregiver request (3%), complete response (2%), and other reasons (13%). The real-world overall response rate for tafa was 76% (95% confidence interval [CI], 69-82%), with a real-world complete response rate of 18% (95% CI, 13-24%). The real-world progression-free survival probability at 6 months post tafa initiation was 0.8 (95% CI, 0.7-0.8). At the time of data collection, most patients were still alive (80%), among whom 84% were still receiving tafa. Conclusions: Findings from this real-world analysis support the clinical benefit of tafa when used in early lines of treatment for R/R DLBCL, as demonstrated in L-MIND. Importantly, the patient population included in this study was racially and ethnically diverse, with nearly one-third of patients from typically underrepresented racial groups and approximately one-sixth of Hispanic ethnicity. Further, this population consisted of patients treated predominantly in a community oncology setting, which is the treatment setting for the majority of patients with DLBCL in the US. Most patients were still on tafa at the time of data collection and follow-up was limited in duration; the median time to complete response in L-MIND (Duell J, et al. Haematologica. 2021;106:2417-2426) was longer than the median follow-up time in this study. Therefore, longer follow-up of these patients is warranted to better understand long-term outcomes of tafa among this diverse patient population.