To quantify excess clonal plasma cell risk and test the hypothesis that cumulative Gaucher disease-specific therapy is associated with reduced incident monoclonal gammopathy.
Approach:
Study Design: A retrospective longitudinal cohort study of adult patients with Gaucher disease, excluding those with pre-existing monoclonal gammopathy.
Clinical Follow-Up: Patients were followed with clinical evaluations every 6–12 months, and serum protein studies were performed to monitor for monoclonal gammopathy.
Treatment Exposure: Gaucher-specific therapy included enzyme replacement therapy and substrate reduction therapy, initiated for systemic disease indications, independent of clonal outcomes.
Outcome Definition: The primary outcome was incident monoclonal gammopathy, confirmed by serum protein electrophoresis with immunofixation.
Statistical Analysis: Cox proportional hazards regression was used to analyze the relationship between therapy exposure and the development of monoclonal gammopathy.
Key Findings:
Cumulative Gaucher-specific therapy was associated with a reduced risk of developing monoclonal gammopathy.
The study design minimized prevalent case bias and reverse causation.
Treatment decisions were independent of clonal plasma cell findings.
Interpretation:
Limitations:
The study is retrospective and may be subject to biases inherent in observational studies.
Direct genomic evidence for mutational signatures in human Gaucher disease-associated monoclonal gammopathy is lacking.
by Noor Ul Ain, Noffar Bar, Lilu Guo, Katherine Klinger, Punita Gupta, Atta Ur Rahman, Ruhua Yang, Yanhong Deng, Natalia Neparidze, Shiny Nair, Pramod K. Mistry
