Bispecific antibody combination regimens for B-cell non-Hodgkin's lymphomas

Bispecific antibodies (BsAbs) are a novel class of immunotherapy agents that engage endogenous T cells to target and eradicate malignant B cells by simultaneously binding CD3 and CD20. BsAbs such as epcoritamab, glofitamab, and mosunetuzumab have demonstrated substantial efficacy across both aggressive and indolent B-cell non-Hodgkin lymphomas (B-NHL), with largely manageable safety profiles. Their off-the-shelf administration offers a practical alternative to CAR T-cell therapy, particularly for patients who are transplant-ineligible or lack access to cellular approaches.

This review provides a comprehensive overview of BsAbs in B-NHL. We detail pivotal studies in relapsed/refractory (R/R) DLBCL, FL, and MCL, highlighting single-agent outcomes and emerging combination strategies. Approaches incorporating BsAbs into cytotoxic backbones and antibody-drug conjugates, as well as chemotherapy-free regimens such as BsAbs combined with lenalidomide, are discussed. We also examine their potential to address poor-risk disease features and historically refractory subsets.

BsAbs represent a major advance in B-NHL, offering high rates of deep remission with predictable safety and outpatient feasibility. As trial data continues to mature, BsAb-based regimens are poised to become foundational across multiple lines of therapy, reshaping expectations for patients with both aggressive and indolent lymphomas.