Recent advances in CD5⁺ diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin's lymphoma (NHL), is substantially heterogeneous. Approximately 5-10% of DLBCLs express CD5, which makes CD5⁺ DLBCL a rare subgroup. Different studies have shown that CD5⁺ DLBCL patients are often older and female and have higher lactate dehydrogenase levels, an Eastern Cooperative Oncology Group (ECOG) performance status > 1, and higher International Prognostic Index (IPI) scores. Moreover, patients often have advanced stage disease with a high incidence of central nervous system (CNS) relapse and bone marrow involvement. CD5⁺ DLBCL cells are more likely to express MYC, BCL-2, and MUM-1, less likely to express CD10, and most belong to the activated B-cell-like (ABC) subtype. The potential mechanisms underlying the poor prognosis of CD5⁺ DLBCL patients may be related to CD5-mediated B-cell receptor (BCR)-dependent and -independent pathways. The efficacy of the traditional rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen is unsatisfactory in CD5⁺ DLBCL patients. Despite supporting evidence from retrospective studies, it is currently unclear whether dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) can improve outcomes in this population. Several new drugs, such as Bruton tyrosine kinase inhibitors (BTKi), BCL-2 inhibitors, and CXCR4 antagonists, as well as immunotherapy, may help to improve the prognosis of CD5⁺ DLBCL patients, but additional clinical explorations are needed to determine the optimal therapeutic strategy for this disease.