In the present review, we address the role of autologous stem cell transplantation (ASCT) and newly approved and established options for the treatment of patients with refractory or relapsed (R/R) DLBCL, such as CD19-targeted chimeric antigen receptor (CAR) T-cells, polatuzumab vedotin combined with rituximab and bendamustine (pola-RB), and tafasitamab combined with lenalidomide. This evidence concerns the gene CD19 and diffuse large B-cell lymphoma.