A Prospective Study of Familial Predisposition in Plasma Cell Dyscrasias

Plasma cell dyscrasias (PCDs) exhibit familial aggregation, yet data quantifying this risk through active screening remains 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 1,084 consecutive patients with PCDs at a single center between 2017 and 2019, of which 864 eligible index patients consented to first- and second-degree relatives 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 2,481 family members were screened; median age 63 years. At least one additional family member with a monoclonal gammopathy 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 families. Notably, the screening process identified 41 new cases of monoclonal gammopathies (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 for PCDs, revealing that over 11% of affected families have multiple members with monoclonal gammopathies, 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.