<p>In patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) who are either refractory to first-line therapy or relapse within 12 months, chimeric antigen receptor (CAR) T-cell therapy is more effective than salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) as second-line therapy. Adoption of CAR T-cell therapy into routine clinical practice involves a period of adaptation and refinement of clinical processes. We aimed to document the evolution of clinical processes for CAR T-cell therapy during 2022 and 2023, and compare healthcare resource utilization (HCRU) associated with CAR T-cell and ASCT processes in routine clinical practice. ClipMed^PPM software-based process modeling was used to assess HCRU for patients with R/R LBCL receiving CAR T-cell or ASCT therapy, mapping 991 and 1174 processes associated with CAR T-cell therapy in 2023 and 2022, respectively, and 1874 processes associated with ASCT over both years. Improvements in lymphodepletion therapy administration and assessment and management of CAR T-cell therapy-specific adverse events led to a 5-day (30%) reduction in hospitalization and a 15% decrease in total personnel time in the CAR T-cell therapy process from 2022 to 2023. HCRU for CAR T-cell therapy was almost half that of ASCT, with 77% less personnel time for therapy administration. Hospitalization for CAR T-cell therapy was 70%-75% shorter than for ASCT therapy (11–13 vs. 44 days). These patient-centered process efficiencies provide patients with reduced hospitalization time. Understanding this evolution is vital for addressing complexities of advanced treatments, enhancing patient care quality, and optimizing resource allocation.</p>