Bispecific Antibodies: A Review of Development, Clinical Efficacy and Toxicity in B-Cell Lymphomas

Abstract

The treatment landscape of B-cell lymphomas is evolving with the advent of novel agents including immune and cellular therapies. Bispecific antibodies (bsAbs) are molecules that recognise two different antigens and are used to engage effector cells, such as T-cells, to kill malignant B-cells. Several bispecific antibodies have entered early phase clinical development since the approval of the CD19/CD3 bispecific antibody, blinatumomab, for relapsed/refractory acute lymphoblastic leukaemia. Novel bsAbs include CD20/CD3 antibodies that are being investigated in both aggressive and indolent non-Hodgkin lymphoma with encouraging overall response rates including complete remissions. These results are seen even in heavily pre-treated patient populations such as those who have relapsed after chimeric antigen receptor T-cell therapy. Potential toxicities include cytokine release syndrome, neurotoxicity and tumour flare, with a number of strategies existing to mitigate these risks. Here, we review the development of bsAbs, their mechanism of action and the different types of bsAbs and how they differ in structure. We will present the currently available data from clinical trials regarding response rates, progression free survival and outcomes across a range of non-Hodgkin lymphoma subtypes. Finally, we will discuss the key toxicities of bsAbs, their rates and management of these adverse events.

Keywords: B-cell lymphoma; bispecific antibodies; cytokine release syndrome; diffuse large B-cell lymphoma (DLBCL); immune cell therapy; neurotoxicity; tumour flare.

Figure 1

Encephalopathy screening tool–Immune Effector Cell-Associated Encephalopathy (ICE) score, adapted from Lee et al. [30]. Score of 10—no impairment; score of 7–9—grade 1 ICANS; score of 3–6—grade 2 ICANS; score of 0–2—grade 3 ICANS; score of 0 due to patient being unarousable and unable to perform assessment–grade 4 ICANS.