Novel monoclonal antibodies for diffuse large B-cell lymphoma

Abstract

Novel immunotherapeutic approaches to the treatment of diffuse large B-cell lymphoma (DLBCL), including recent approvals of chimeric antigen receptor T-cell therapy, the antibody-drug conjugates polatuzumab vedotin (PV) and loncastuximab tesirine-lpyl, and the anti-CD19 antibody tafasitamab, provide efficacious new treatment options for patients with relapsed and refractory disease. PV was the first novel therapy approved in combination with bendamustine/rituximab (BR) for relapsed/refractory (r/r) DLBCL patients after two or more lines of treatment who are ineligible for high-dose chemotherapy and autologous hematopoietic cell transplantation. This approval was based on a randomized phase II study comparing PV-BR versus BR arms, resulting in significantly improved rates of complete metabolic response, progression-free survival, and overall response (OS). Remarkably, this was the first randomized study in DLBCL demonstrating OS benefit to an experimental arm to have been conducted in several years. The promising activity of PV-BR in rrDLBCL may be a result of the use of innovative target CD79b that enables the bypassing of resistance mechanisms related to the CD20 molecule. Two other recently approved antibodies are directed to CD19 antigen, the other attractive alternative target in lymphoma. Although these agents are generally approved for use as third- or second-line therapy, studies are in progress exploring their value in earlier treatment lines including induction treatment. While we still await the successful incorporation of other targeted agents into the treatment of DLBCL, R-CHOP prevails as the standard of care for DLBCL, regardless of immunohistochemical or molecular subtype at diagnosis.