The Role of CAR-T Cell Therapy As Second Line in Diffuse Large B-cell Lymphoma

For approximately three decades, autologous hematopoietic cell transplantation (auto-HCT) has been the standard of care for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after frontline therapy. This approach is limited due to the intensity of chemotherapy and the proportion of patients who relapse after auto-HCT. Since the approval of anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy and novel agents, the treatment paradigm for DLBCL has changed remarkably. Anti-CD19 CAR-T therapy was first approved for relapsed DLBCL after two or more previous lines of therapy with long-lasting responses, with over 50% of patients still alive at 5-year follow-up. Here, we discuss recent randomized phase 3 clinical trials using axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel in the second-line therapy setting compared with the standard of care in transplant-eligible patients who have DLBCL R/R within 12 months of completing chemo-immunotherapy, potentially changing the treatment algorithm for DLBCL.