New drugs for the management of relapsed or refractory diffuse large B-cell lymphoma

Clémentine Sarkozy, Laurie H. Sehn


Approximately 65% of patients with diffuse large B-cell lymphoma (DLBCL) can be cured with standard front-line therapy and achieve an overall survival comparable to the general population. Of the 35% of patients who fail front-line therapy, less than a quarter can be salvaged and cured by intensive chemotherapy followed by an autologous stem cell transplant. Patients who are transplant-ineligible (including elderly patients with co-morbidities, patients who are chemotherapy-refractory or those who have failed transplant) represent an unmet medical need population with a very poor outcome. While chimeric antigen receptor T-cell (CAR-T) therapy has shown promise in this setting, many patients will be unsuitable or relapse after CAR-T therapy. These patients are ideal candidates for less toxic novel therapies and a more tailored personalized approach, recognizing the biological heterogeneity of DLBCL. In this review, we will briefly summarize the standard management options for relapsed/refractory DLBCL and then focus on the novel therapies currently in development. We aim to discuss the biological rationale and available clinical data for the most promising agents, including monoclonal antibodies, antibody-drug conjugates (ADC), pathway inhibitors, immunomodulatory agents and epigenetic modifiers.