T-cell/histiocyte-rich large B-cell lymphoma, insights into prognosis and treatment complexity in the context of immunotherapeutics.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare and biologically distinct subtype of diffuse large B-cell lymphoma (DLBCL). It is marked by rare neoplastic B-cells within a prominent inflammatory microenvironment. Historically it was associated with poor prognosis but contemporary reports show outcomes comparable if not better than DLBCL-NOS, especially with the use of chemo-immunotherapies. Autologous stem cell transplantation (auto-HCT) demonstrated favorable progression-free and overall survival in relapsed patients in comparison to matched DLBCL cohorts. The efficacy of CD19-directed CAR T-cell therapy in THRLBCL has been limited, with high relapse rates and poor durability of response, likely due to an immunosuppressive tumor microenvironment characterized by PD-1/PD-L1 pathway activation. Several case series and translational studies support the use of immune checkpoint blockade in selected patients, although prospective validation is needed. While bispecific antibodies, tafasitamab-lenalidomide, and antibody-drug conjugates show promise in R/R DLBCL, THRLBCL patients remain underrepresented in these pivotal trials. This review summarizes current insights into the prognosis of THRLBCL and underscores the need for novel, biologically informed strategies to improve outcomes in the relapsed setting through a deeper understanding of its biology and immune evasion mechanisms.