Current options and future perspectives in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of aggressive lymphoma. Depending on individual risk factors, roughly 60-65% of patients can be cured by chemoimmunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, patients with primary refractory disease or relapse (R/R) after an initial response are still characterized by poor outcome. Until now, transplant-eligible R/R DLBCL patients are treated with intensive salvage regimens followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) which, however, only cures a limited number of patients. It is most likely that in patients with early relapse after chemoimmunotherapy, chimeric antigen receptor (CAR) T-cells will replace high-dose chemotherapy and ASCT. So far, transplant-ineligible patients have mostly been treated in palliative intent. Recently, a plethora of novel agents comprising new monoclonal antibodies, antibody drug conjugates (ADC), bispecific antibodies, and CAR T-cells have emerged and have significantly improved outcome of patients with R/R DLBCL. In this review, we summarize our current knowledge on the usage of novel drugs and approaches for the treatment of patients with R/R DLBCL.