Male sex adversely impacts survival and myeloid malignancy risk in MGUS: a real-world population-based study

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is a common plasma cell disorder with well described risks of progression to myeloma and lymphoplasmacytic lymphoma. Using data from an established UK population-based cohort of haematological malignancies and premalignancies, we investigated patient and disease characteristics, subsequent haematological malignancy, and survival in 4651 people diagnosed with MGUS 2005-2019. The 5-year net (relative) survival (disease-specific estimate of the probability of survival) of MGUS patients was 87.8% (95% Confidence Interval 85.9-89.7), with males (83.8%; 95% CI 81.0-86.6) more affected than females (92.2%; 95% CI 89.7-94.7). The proportion of subsequent haematological malignancies was also higher in males than females (8.8% versus 5.3%; P<0.001); the average annual rates of transition being 1.81 (95% CI 1.44-218) and 0.99 (95% CI 0.72-1.27) respectively. Furthermore, whilst annual rates of transformation to myeloma (1.04%) and lymphoplasmacytic lymphoma (0.11%) were as expected, both were higher in males (1.23% and 1.18%) than females (0.8% and 0.06%). With a median time to diagnosis of 40 months, the incidence of myeloid malignancy was also raised in males (Relative Risk 3.6, 95% CI 2.5-4.9), but not females (RR=1.0, 95% CI 0.3-1.9). No associations between MGUS and subsequent development of chronic lymphocytic leukaemia were observed. Providing new data on the nature of MGUS progression, our analyses revealed previously undescribed sex disparities; including worse survival and increased rates of myeloid malignancy in males with non-IgM MGUS. These findings have implications for future research, as well as risk stratification and monitoring of patients with this highly prevalent plasma cell dyscrasia.