Bispecific antibody combination therapies in diffuse large B-cell lymphoma

Bispecific T-cell-engaging antibodies (TCEs) are a significant advance in the treatment of diffuse large B-cell lymphoma (DLBCL), demonstrating robust clinical activity with manageable toxicity profiles. Their integration into third line as monotherapy, and now second line in combination, as well as recent data in the first line underscores their therapeutic potential. The efficacy of bispecific antibodies depends on sustained target antigen expression and preserved T-cell function; the loss of either of these factors, or intrinsic tumour and microenvironment biology, contributes to therapeutic resistance. Combination strategies aim to overcome these resistance mechanisms, enhance anti-tumour efficacy and potentially reduce treatment-related adverse events. In this review, we critically examine the current understanding of TCE resistance and discuss how this informs combination strategies. We explore approaches to bispecific antibody-based combination therapies in DLBCL and review emerging clinical trial results, with a view on potential future strategies for TCE-based combinations.