Serum Paraprotein Is Associated with Adverse Prognostic Factors and Outcome, across Different Subtypes of Mature B-Cell Malignancies—A Systematic Review

SIMPLE SUMMARY: This systematic review encompasses the clinical impact of serum paraprotein (PP), in low- and high-grade mature B-cell malignancies (except for myeloma and Waldenstrom Macroglobulinemia). In fact, reports on this topic are sparse and heterogeneous, and an overall view is lacking. Literature analysis shows that, across different entities, PP is consistently associated with high-risk biological and clinical features, as well as with poor outcome. Indeed, screening for serum PP should be included in the diagnostic work-up of all mature B-cell malignancies. ABSTRACT: The presence of a serum paraprotein (PP) is usually associated with plasma-cell dyscrasias, Waldenstrom Macroglobulinemia/lymphoplasmacytic lymphoma, and cryoglobulinemia. However, PP is also often reported in other high- and low-grade B-cell malignancies. As these reports are sparse and heterogeneous, an overall view on this topic is lacking, Therefore, we carried out a complete literature review to detail the characteristics, and highlight differences and similarities among lymphoma entities associated with PP. In these settings, IgM and IgG are the prevalent PP subtypes, and their serum concentration is often low or even undetectable without immunofixation. The relevance of paraproteinemia and its prevalence, as well as the impact of IgG vs. IgM PP, seems to differ within B-NHL subtypes and CLL. Nonetheless, paraproteinemia is almost always associated with advanced disease, as well as with immunophenotypic, genetic, and clinical features, impacting prognosis. In fact, PP is reported as an independent prognostic marker of poor outcome. All the above call for implementing clinical practice, with the assessment of paraproteinemia, in patients’ work-up. Indeed, more studies are needed to shed light on the biological mechanism causing more aggressive disease. Furthermore, the significance of paraproteinemia, in the era of targeted therapies, should be assessed in prospective trials.