Inflammation and infection in plasma cell disorders: how pathogens shape the fate of patients

Abstract

The role of infection and chronic inflammation in plasma cell disorders (PCD) has been well-described. Despite not being a diagnostic criterion, infection is a common complication of most PCD and represents a significant cause of morbidity and mortality in this population. As immune-based therapeutic agents are being increasingly used in multiple myeloma, it is important to recognize their impact on the epidemiology of infections and to identify preventive measures to improve outcomes. This review outlines the multiple factors attributed to the high infectious risk in PCD (e.g. the underlying disease status, patient age and comorbidities, and myeloma-directed treatment), with the aim of highlighting future prophylactic and preventive strategies that could be implemented in the clinic. Beyond this, infection and pathogens as an entity are believed to also influence disease biology from initiation to response to treatment and progression through a complex interplay involving pathogen exposure, chronic inflammation, and immune response. This review will outline both the direct and indirect role played by oncogenic pathogens in PCD, highlight the requirement for large-scale studies to decipher the precise implication of the microbiome and direct pathogens in the natural history of myeloma and its precursor disease states, and understand how, in turn, pathogens shape plasma cell biology.

Monitoring, prophylaxis, and treatment of infections in patients with MM receiving bispecific antibody therapy: consensus recommendations from an expert panel

“…In addition, MM, a disease of the immune system, is frequently associated with significant immune impairment and dysfunction of the adaptive immune response, due to malfunction of the immune regulation of plasma cells [ 29 ]. This results in an increased risk of infections in this population [ 30 ].…”

COVID-19 in multiple myeloma patients: frequencies and risk factors for hospitalization, ventilatory support, intensive care admission and mortality –cooperative registry from the Grupo Brasileiro de Mieloma Multiplo (GBRAM)

“… 7 Infection complications are frequent at diagnosis and remain clinically significant during all phases of treatment. 1 , 2 , 8 …”

An elevated systemic inflammation index is related to an inferior response to pomalidomide and dexamethasone treatment in patients with relapsed and refractory multiple myeloma

“…Inflammation is known to promote cell proliferation and survival, and thus tumour growth [ 28 ]. It has been proposed that an aberrant immune response, directed at either self-proteins or pathogens, heightens the chances of genetic changes and consequent transformation into MM [ 29 ]. Persistent antigenic stimulation might also induce genomic instability in MM by activating cytidine deaminases, a mechanism proposed to elucidate the transition from smouldering MM to MM [ 30 ].…”