Bispecific antibody therapy, its use and risks for infection: Bridging the knowledge gap

Abstract

Relapsed haematological malignancies have a poor disease prognosis with current therapies. Bispecific antibodies (BsAbs) are becoming increasingly recognised for their efficacy in the treatment of these malignancies and are approved for the treatment of B-cell acute lymphoblastic leukaemia (B-ALL). BsAbs are manufactured to consist two variable chain fragments combined by a peptide linker amongst other structures to increase the half-life of the molecules. BsAbs function by bringing targeted tumour cells in close proximity of T-cells to allow killing via perforin and granzyme release. The increasing numbers of trials of BsAbs has highlighted their toxicity profile, including cytokine release syndrome (CRS), cytopaenia and hypogammaglobulinemia - which all increase risks for infection. The patterns and risks for infections with these novel agents remain unclear. This review article provides an overview of the risks of infection with various BsAbs platforms. A review of clinical trials reveals rates of infections amongst patients on BsAbs between 15 and 45% with a high proportion grade 3 severity or higher. A predominance of bacterial respiratory and line-related infections were identified amongst all haematological malignancies. In particular, high rates of febrile neutropaenia were identified in use of BsAbs in myeloid malignancy. Infection patterns identified in this review are utilised to inform infection prevention practice, including focused infection screening, line management, prophylaxis and vaccination strategies. Prophylaxis strategies against Pneumocystis pneumonia, herpes simplex and herpes zoster, candida and mould infections are considered, along with vaccination strategies against respiratory viral and bacterial infections. The long-term impacts of BsAbs on the immune system continue to be established.

Keywords: Bi-specific antibodies; Immunocompromised; Infection; Risks.