The potential of antibody-drug conjugates for effective therapy in diffuse large B-cell lymphoma

Antibody-drug conjugates (ADCs) are a rapidly evolving class of anti-cancer drugs with a significant impact on management of hematological malignancies including diffuse large B-cell lymphoma (DLBCL). ADCs combine a cytotoxic drug (a.k.a. payload) attached through a linker to a monoclonal antibody specific to a particular cancer antigen. Payloads include microtubule disruptors or DNA damaging chemicals. After attaching to the antigen, the ADCs are internalized, and the payload is dissociated from ADC by lysozymes and delivered to the intended site for exerting cytotoxic effects. This unique molecular design permits a better balance of efficacy and safety. Loncastuximab tesirine and polatuzumab vedotin are two ADCs approved in the U.S.A. for treatment of DLBCL.

This review covers the efficacy and safety data of these two drugs. We will review new ADC-based combination regimens and novel constructs in development.

ADCs have made a significant impact in improving outcomes of DLBCL patients. Both polatuzumab vedotin and loncastuximab tesirine are established as useful therapeutics options, with polatuzumab vedotin currently approved in first line and relapsed/refractory setting, while loncastuximab tesirine is approved in relapsed setting. ADCs are effective with tolerable safety profile and currently many more ADCs are undergoing clinical trials.