Monoclonal gammopathies and hypergammaglobulemia in Gaucher disease: an analysis from the French Gaucher disease registry

Objectives: To determine the risk factors, the clinical significance, and the evolution of monoclonal gammopathy (MG) and hypergammaglobulinemia (HG) in Gaucher disease (GD). Methods: Patients from the French GD Registry with information on the presence or absence of MG and HG (defined by an immunoglobulin level above 15 g/L) at baseline and/or during follow-up were studied retrospectively. The characteristics at diagnosis and the first occurrence of MG, HG, bone events and severe thrombocytopenia during follow-up were collected. The risk factors of developing MG/HG and the association between MG/HG with disease severity were analyzed using log-rank tests and multivariable Cox proportional hazards models, using MG/HG and bone events/severe thrombocytopenia as events, respectively. Effect of treatment on gammaglobulin levels was assessed using linear/logarithmic mixed models. Results: 59/187 patients (31.6%) had MG: 20 (33.9%) at diagnosis of GD and 39 (66.1%) during follow-up after 19.0 ± 11.0 years following diagnosis. 112/235 (47.7%) had HG: 15 (13.5%) at diagnosis of GD and 96 (86.5%) during follow-up. Mean ± SD age at diagnosis of MG and HG were 49.7 ± 14.3 and 35.0 ± 16.5 years, respectively. Multivariable analysis (hazard ratio 95% confidence interval) retained age at diagnosis of GD as the unique independent risk factor for MG (1.08 1.05-1.10). MG or HG were neither associated with the occurrence of bone events ([1.11 0.52-2.36] and [1.16 0.64-2.11], respectively), nor severe thrombocytopenia ([0.89 0.25-3.13] and [1.17 0.54-2.54], respectively). During follow-up, 5/187 had lymphomas (1 following MG and 3 following HG) and 1/187 multiple myeloma (following MG). Under treatment, immunoglobulin levels significantly decreased (slope = -0.24 [95%CI, -0.28, -0.20] per year, P Conclusion: MG and HG are not associated with unfavorable outcome in GD but should encourage monitoring of hematologic malignancies.