A prospective study of familial predisposition to plasma cell dyscrasias

Plasma cell dyscrasias (PCDs) exhibit familial aggregation, yet data quantifying this risk through active screening remain limited. Herein, we designed this study to identify and quantify the familial risk of PCDs by detailed family trees and screening all first- and second-degree relatives of affected patients. We approached 1084 consecutive patients with PCDs at a single center between 2017 and 2019, of whom 864 eligible index patients provided consent to first- and second-degree relative screening. Detailed pedigrees were created for all patients, and screening with serum protein electrophoresis, immunofixation, and free light chain assays was performed. Spouses were also screened as a control group. In total, 2481 family members were screened; median age was 63 years. At least 1 additional family member with a monoclonal gammopathy (MG) was detected in 98 (11.3%) of the 864 screened families. A positive history of PCD or other B-cell malignancy was present in 2.1% of the families. Notably, the screening process identified 41 new cases of MGs (4.7% yield per family). The incidence was 4.5% among siblings and second-degree relatives compared to 2.6% in the control group. In conclusion, this large prospective study confirms a familial predisposition to PCDs, revealing that >11% of the affected families have multiple members with MGs, corresponding to at least twice the risk of PCDs among members of affected families. These findings support the potential clinical value of active screening for relatives of patients with PCDs to facilitate early diagnosis, appropriate monitoring, and prompt intervention.