Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma...

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Antibody drug conjugates (ADCs) are novel therapeutic agents for lymphomas.
• Pinatuzumab vedotin (anti-CD22 ADC) and polatuzumab vedotin (anti-CD79B ADC) utilize monomethyl auristatin E (MMAE) as a cytotoxic payload.
• Diffuse large B-cell lymphoma (DLBCL) comprises distinct molecular subtypes, including activated B-cell-like (ABC) and germinal center B-cell-like (GCB).

Purpose of the Study:

• To evaluate the efficacy of anti-CD22-MMAE and anti-CD79B-MMAE in various DLBCL molecular subtypes.
• To assess the activity of these ADCs in both in vitro and early clinical settings.
• To determine the correlation between target antigen expression and treatment response.

Main Methods:

• In vitro analysis of ADC activity in DLBCL cell lines representing ABC and GCB subtypes.
• Assessment of ADC cytotoxicity in models with and without CD79B mutations.
• Evaluation of patient responses in early clinical trials for relapsed and refractory DLBCL.

Main Results:

• Both anti-CD22-MMAE and anti-CD79B-MMAE demonstrated high activity and induced cell death in the majority of DLBCL cell lines.
• Cytotoxicity was observed in models regardless of CD79B mutation status.
• Relapsed and refractory DLBCL patients, across subtypes, responded positively to both ADC agents.
• No strong correlation was found between CD22/CD79B expression and in vitro/in vivo activity, suggesting broad applicability.

Conclusions:

• Pinatuzumab vedotin and polatuzumab vedotin are active therapeutic agents for diverse DLBCL subtypes.
• Target expression levels should not preclude patients from receiving these ADC treatments.
• These ADCs represent promising options for patients with relapsed or refractory DLBCL.