Monoclonal Antibodies in the Treatment of Diffuse Large B-Cell Lymphoma: Moving beyond Rituximab

SIMPLE SUMMARY: Diffuse large B-cell lymphoma (DLBCL) is the most common high-grade non-Hodgkin lymphoma. The current treatment combining the anti-CD20 monoclonal antibody rituximab with chemotherapy is the gold standard for frontline treatment. Although the results for patients who relapse had been disappointing, the recent research explosion on novel agents for DLBCL has reignited the hope for these patients. This review aims to summarize the exciting research results of novel therapeutic agents recently approved or under investigation for the treatment of DLBCL. We focus on novel monoclonal antibodies conjugated to cytotoxic drugs and bispecific antibodies that have shown very promising results for patients in the relapsed/refractory setting. ABSTRACT: Although rituximab has revolutionized the treatment of diffuse large B-cell lymphoma (DLBCL), a significant proportion of patients experience refractory disease or relapse early after the end of treatment. The lack of effective treatment options in the relapsed/refractory (R/R) setting had made the prognosis of these patients dismal. The initial enthusiasm for novel anti-CD20 antibodies had been short-lived as they failed to prove their superiority to rituximab. Therefore, research has focused on developing novel agents with a unique mechanism of action. Among them, two antibody-drug conjugates, namely polatuzumab vedotin (PolaV) and loncastuximab tesirine, along with tafasitamab, an anti-CD19 bioengineered antibody, have been approved for the treatment of R/R DLBCL. Whereas PolaV has been FDA and EMA approved, EMA has not approved loncastuximab tesirine and tafasitamab yet. Results from randomized trials, as well as real-life data for PolaV have been promising. Novel agents as bispecific antibodies bridging CD3 on T-cells to CD20 have shown very promising results in clinical trials and are expected to gain approval for treatment of R/R DLBCL soon. As the therapeutic armamentarium against DLBCL is expanding, an improvement in survival of patients with R/R and higher cure rates might soon become evident.