Anti-CD20 monoclonal antibodies in chronic lymphocytic leukaemia: Mechanisms, resistance, and the evolution of targeted immunotherapy

Abstract

Anti-CD20 monoclonal antibodies (mAbs) have been the gold standard in the treatment of B-cell malignancies since their inception, most notably in the case of rituximab and related chimeric antibodies. However, a particular subtype of non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukaemia (CLL), has shown comparatively poor outcomes. Its slow-paced, indolent nature makes diagnosis difficult, while its evasive nature complicates therapy. The rise in the incidence of CLL, in South Africa in particular, has emphasised the need for ongoing research. Despite the availability of revolutionary therapies that have transformed outcomes in other NHL subtypes, treatment of CLL remains largely experimental. A comprehensive and systematic literature review was therefore conducted to illustrate the impact of anti-CD20 and to explore potential avenues for improvement in the field. Studies illustrate that the treatment landscape has grown considerably, from the introduction of newer mAbs such as obinutuzumab to altogether different modalities such as bispecifics, chimeric antigen receptor (CAR) T cells, and even a combination of these immunotherapy regimens. However, the largely experimental nature of these strategies and the ability of CLL to manufacture its tumour microenvironment continue to limit progress. It is evident that although great strides have been made, future breakthroughs via exploitation of the molecular pathways and mutations driving CLL will be essential to refine therapeutic approaches and advance the treatment of CLL and B-cell malignancies more broadly.