Abstract
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.
Overview
- The study reviews the efficacy and safety data of two antibody-drug conjugates (ADCs), loncastuximab tesirine and polatuzumab vedotin, approved in the US for treating diffuse large B-cell lymphoma (DLBCL).
- The ADCs combine a cytotoxic drug (payload) attached to a monoclonal antibody specific to a cancer antigen, allowing for targeted delivery of the payload to the intended site.
- The study aims to discuss new ADC-based combination regimens and novel constructs in development, as well as the significant impact ADCs have made in improving outcomes for DLBCL patients.
Comparative Analysis & Findings
- The study compares the efficacy and safety profiles of loncastuximab tesirine and polatuzumab vedotin in treating DLBCL, with both drugs showing effective and tolerable safety profiles.
- Polatuzumab vedotin is currently approved in both first-line and relapsed/refractory settings, while loncastuximab tesirine is approved in relapsed/refractory setting.
- The study highlights the potential of ADCs in improving outcomes for DLBCL patients, with many more ADCs undergoing clinical trials.
Implications and Future Directions
- The study emphasizes the significant impact ADCs have made in improving outcomes for DLBCL patients, and their potential to revolutionize treatment options.
- Future studies should focus on developing new ADC-based combination regimens and novel constructs to further improve treatment outcomes.
- Investigating the safety and efficacy profiles of ADCs in different patient populations and treatment settings is also crucial for future research.