Up to 40% of patients with diffuse large B-cell lymphoma (DLBCL) will have relapsed/refractory (R/R) disease after first-line (1L) treatment with R-CHOP. Treatment options for autologous stem cell transplant (ASCT)-ineligible patients with R/R DLBCL include the chemo-free immunotherapy tafasitamab + lenalidomide, polatuzumab + bendamustine + rituximab, loncastuximab tesirine, selinexor, and CD19 chimeric antigen receptor (CAR) T-cell therapies. Treatment sequencing and identifying the optimal choice for individual patients can be challenging for oncologists. realMIND (NCT04981795) will assess real-world treatment patterns, effectiveness measures, and patient-reported outcomes among patients in the United States (US) with R/R DLBCL not receiving ASCT. A Phase IV, prospective, multicenter, observational study enrolling a diverse patient population with R/R DLBCL regarding age, ethnicity, and race. Expected enrollment is ~1000 patients with completion expected ~79 months after the first patient is enrolled. Actively recruiting in ~75 US community and academic centers. Eligible and aged ≥18 years with histologically confirmed R/R DLBCL after ≥1 systemic therapy, including ASCT. Patients may enroll (a) after completing 1L therapy and before starting second-line (2L) therapy, (b) within 30 days after starting 2L therapy, or (c) after completing 2L and before receiving third-line therapy. Patient history data on therapies received before study enrollment will be collected from patient records; data generated from the time of enrollment onwards will be collected prospectively. Real-world effectiveness measures include complete and objective response rate, duration of response, event-free survival, and overall survival; safety endpoints include serious adverse events and adverse events leading to treatment discontinuation, interruption, or dose modification. Patient-reported outcomes include general and lymphoma-specific measures of health-related quality of life assessed by the EORTC Quality of Life Questionnaire-Core 30 and Functional Assessment of Cancer Therapy - Lymphoma, and work productivity by the Work Productivity and Activity Impairment Questionnaire. Not yet available. realMIND will characterize the R/R DLBCL patient journey with respect to treatment patterns, clinical and patient-reported outcomes. The study population will reflect a representative patient distribution within the US, facilitating the investigation of outcomes reflecting real-world clinical practice and producing data to support healthcare decision-making. MorphoSys AG.