Refractory DLBCL: Challenges and Treatment.

Despite a greater understanding of pathologic factors that increase the chance for treatment failure, initial therapy of diffuse large B cell lymphoma (DLBCL) has not evolved from R/CHOP. Although it was anticipated that the genetic underpinnings of the cell or origin would dramatically change treatment, thus far, this has not been realized. Similarly, contrary to the situation with Hodgkin lymphoma, meaningful early treatment response assessment with PET-CT has yet to be established in DLBCL. Nevertheless, there is tremendous enthusiasm that circulating tumor DNA, possibly in combination with PET- T may facilitate earlier recognition of treatment failure or relapse. And, in contrast to the situation with front-line treatment, therapy for recurrent disease appears to be on the cusp of dramatically improving. Thus, in addition to high dose therapy with autologous transplant, a treatment that is not feasible for many older patients, CAR-T cells, bispecific T-cell engagers (BiTEs), antibody-drug conjugates and new monoclonal antibodies are all offering the possibility of long-term disease control and possible cure. The success of the cell and immunotherapies even offer hope for a chemotherapy-free strategy, initially for recurrent disease. Herein, we review the landscape of the novel agents in resistant DLBCL and speculate about their appropriate sequencing and possible migration to earlier use.