Health impact of monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B-cell lymphocytosis (MBL): findings from a UK population-based cohort

ABSTRACT Objective To examine co-morbidity patterns in individuals with monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B-cell lymphocytosis (MBL), both before and after premalignancy diagnosis; and compare their activity to that of the general population. Design Population-based patient cohort, within which each patient is matched at diagnosis to 10 age and sex-matched individuals from the general population. Both cohorts are linked to nationwide information on deaths, cancer registrations, and Hospital Episode Statistics (HES). Setting The UK’s Haematological Malignancy Research Network; which has a catchment population of around 4 million served by 14 hospitals and a central diagnostic laboratory. Participants All patients newly diagnosed 2009–15 with MGUS (n = 2203) or MBL (n = 561), and their age and sex-matched comparators (n = 27,638). Main Outcome measures Survival, and hospital inpatient and outpatient activity in the five years before, and three years after, diagnosis. Results Individuals with MGUS experienced excess morbidity in the 5-years before diagnosis, and excess mortality and morbidity in the 3-years after. Increased rate-ratios (RR) were evident for nearly all clinical specialties; the largest, both before and after diagnosis, being for nephrology (before RR = 4.38, 95% Confidence Interval 3.99–4.81; after RR = 14.7, 95% CI 13.5–15.9) and rheumatology (before RR = 3.38, 95% CI 3.16–3.61; after RR = 5.45, 95% CI 5.09–5.83). Strong effects were also evident for endocrinology, neurology, dermatology and respiratory medicine. Conversely, only marginal increases in mortality and morbidity were evident for MBL. Conclusions From a haematological malignancy perspective, MGUS and MBL are generally considered to be relatively benign. Nonetheless, monoclonal gammopathy has the potential to cause systemic disease and wide-ranging damage to most organs and tissues. Hence, even though most people with monoclonal immunoglobulins never develop a B-cell malignancy or suffer from any other form of M-protein related organ/tissue related disorder, the consequences for those that do can be extremely serious.