Introduction: Diffuse large B cell lymphoma (DLBCL) is the most frequent lymphoma in adults. 30-40% DLBCL eventually relapse and 10% are primary refractory, posing an unmet clinical need, especially in patients not eligible for hematopoietic stem cell transplant. Knowledge of DLBCL molecular pathogenesis has identified druggable molecular pathways. Surface antigens can be targeted by novel antibodies and innovative cell therapies. Areas covered: This review illuminates those investigational drugs and cell therapies that are currently in early phase clinical trials for the treatment of DLBCL. New small molecules that modulate the pathways involved in the molecular pathogenesis of DLBCL, monospecific and bispecific monoclonal antibodies, drug-immunoconjugates, and cellular therapies are placed under the spotlight. A futuristic perspective concludes the paper. Expert opinion: A precision medicine strategy based on robust molecular predictors of outcome is desirable in the development of investigational small molecules for DLBCL. Novel monoclonal and bispecific antibodies may be offered to (i) relapsed/refractory patients ineligible for CAR-T cells because of comorbidities, and (ii) younger patients before CAR-T cell infusion to reduce a high tumor burden. A focus on the optimal sequencing of the emerging DLBCL drugs is appropriate and necessary.
Keywords: Bispecific antibodies; CAR-T cells; cell therapy; diffuse large B cell lymphoma; monoclonal antibodies; small molecules; target therapy.