Antibody Therapies for Large B-Cell Lymphoma

Abstract

Large B-cell lymphomas (LBCLs) constitute a subgroup of aggressive but highly curable lymphoproliferative diseases. Treatment of relapsed/refractory (R/R) patients still represents an unmet clinical need, and novel drugs and combinations are in continuous development. The pan-B cell panel of surface antigens that characterizes LBCL leads to a large umbrella of druggable targets. Monoclonal antibodies (mAbs) express their activity against lymphoma by targeting multiple tumor-specific antigens. This category consists of a number of molecules with different mechanisms of action, including naked mAbs, radioimmunoconjugates, antibody-drug conjugates, checkpoint inhibitors, and bispecific antibodies. In the last decade, apart from the well-known role of the anti-CD20 mAb rituximab, novel mAbs have led to remarkable steps forward in the treatment of R/R LBCL in monotherapy and combined with chemotherapy. Multiple studies are in development trying to bring these novel compounds into the frontline setting to empower the RCHOP effect or as alternative chemotherapy-free options for elderly/unfit patients. This review provides insight into antilymphoma mAbs, focused on the efficacy and safety of the main molecules approved or in development for LBCL andperspectives on the treatment of this disease.

Keywords: bispecific antibodies; checkpoint inhibitors; diffuse large B-cell lymphoma; immunotherapy; monoclonal antibodies; targeted therapy.

Figure 1

Monoclonal antibodies, including naked antibodies, antibody–drug conjugates, radioimmunoconjugates, and bispecific antibodies, are able to target Bcells on different surface antigens and with a number of cytotoxic mechanisms of action.

Figure 2

Checkpoint inhibitors (anti-CD47, anti-PDL1/2, antiCTLA4, and anti-PD1) disrupt interaction between inhibitory receptors and their ligands and thus activate antitumor immunity.