Prognosis of young patients with monoclonal gammopathy of undetermined significance.

Abstract

8049 Background: Monoclonal gammopathy of undetermined significance (MGUS) is rare in young patients (pts; age <40 years at diagnosis), with a prevalence of < 0.3%, representing approximately 2% of all patients with MGUS. We hypothesized that MGUS detected in pts <40 years of age may be associated with a higher risk of progression. Methods: We identified 249 pts with MGUS <40 yrs old, evaluated at Mayo Clinic, Rochester from 1997 to 2016. The endpoint was time to progression assessed by Kaplan-Meier method. Results: 119 were male, 130 were female. Most (n= 179, 72%) were diagnosed between the ages of 30-39. The type of MGUS was IgG 69%, IgA 10%, IgM 15%, and other 5%. 135 pts (54%) had concurrent immune-related conditions, including autoimmune, inflammatory, and infectious disorders at the time of diagnosis of MGUS. Pts without immune-related conditions tend to have higher M protein compared to pts with immune-related conditions (mean, 0.36 gm/dl VS 0.20 gm/dl, p =0.057). During follow up, the M protein resolved in 36 patients. The M protein was more likely to resolve in pts with immune-related conditions compared with pts without immune-related conditions (RR 1.91, 95% CI 1.02-3.59). Progression was seen in 16 pts: 9 smoldering multiple myeloma (SMM), 4 multiple myeloma (MM), 1 macroglobulinemia, 2 non-Hodgkin’s lymphoma. The rate of progression to SMM, MM, or related disorder at 5 and 10 years was 6.0% and 13.8%, respectively. The size of M protein was a significant risk factor for progression (HR 4.23, 95% CI 2.17-7.91) The risk of progression at 5 and 10 years for pts with immune-related conditions concurrently present when MGUS was first diagnosed was 1.5% and 10.1% respectively; corresponding rate in pts without immune-related conditions at the time of diagnosis was higher at 12.3% and 18.9%, respectively (p =0.016), (HR 2.36, 95% CI 0.85-6.52). Similar results were seen when patients in whom the M protein resolved were excluded. Conclusions: Young patients with MGUS may have a higher risk of progression, 1.4% per year; approximately 50% are diagnosed in the setting of immune-related disorders. When occurring in the setting of immune related disorders, the M protein is smaller, more likely to resolve, and may have a lower risk of progression than in pts in whom MGUS is detected without concurrent immune-related disorder.