Pathogenesis and management of immune dysfunction secondary to B cell haematological malignancies

Abstract

Malignancies of the B-lymphocyte lineage are among the most diagnosed haematological malignancies in clinical practice. In our community, multiple myeloma (MM) and its precursor condition monoclonal gammopathy of undetermined significance are the commonest, accounting for ~12% of diagnoses, followed by chronic lymphocytic leukaemia (CLL) and its precursor condition monoclonal B lymphocytosis, ~9%. Along with diffuse large B cell lymphoma, follicular lymphoma and marginal zone lymphoma, these conditions comprise around a third of all haematological malignancies diagnosed. Infection remains an important cause of mortality and morbidity in the management of patients with these conditions. This is in part treatment-related but also reflective of disease-related immune dysfunction. Infectious complications account for up to 50% of early mortality in patients with myeloma and up to 50% of all mortality in patients with CLL. A variety of strategies are available to decrease the morbidity and mortality of infectious complications; however, practices vary between countries and often between treating physicians. Treatment options have evolved significantly over the last decade, with the introduction of monoclonal antibodies, small molecule inhibitors, second- and third-generation immunomodulatory agents and CAR-T cell therapy. Much of the data that inform clinical practice in infection management predates current therapeutic approaches. This is in part because of the rapid development of new therapies but also reflective of the long natural history of many of these diseases and the need for prolonged periods of observation. In this article, we review the aspects of disease and treatment that contribute to immune dysfunction in MM, CLL and B-cell non-Hodgkin lymphoma and review the current strategies used to manage immune dysfunction and infection.

Keywords: CLL; acquired immune deficiency; immune dysfunction; myeloma; non-Hodgkin lymphoma.