Prognostic Relevance of Genomic Aberrations In Light Chain Only Multiple Myeloma

Multiple myeloma (MM) is characterized by an expansion of clonal plasma cells with production of monoclonal immunoglobulin. The majority of MM patients produce an intact immunoglobulin, but in a subset of patients (≂f15%), the tumor produces monoclonal light chains only (LCO). Although specific genomic aberrations have emerged as a major prognostic factor in MM, the genomic changes and their prognostic impact on LCO myeloma patients are not clear.

A total of 86 patients with LCO MM identified by urine and serum immunoelectrophoresis were included in this study. They were all uniformly treated with high dose chemotherapy followed by autologous stem cell transplant (ASCT). The genomic risk factors including del(13q), del(17p), t(4;14), 1q21 gain and 1p loss– were evaluated by cytoplasmic fluorescence in situ hybridization (cIg-FISH) in clonal plasma cells and correlated with patients clinical outcomes.

cIg-FISH detected del(13q) in 41%, t(4;14) in 12%, del(17p) in18%, 1q21 gain in 25%, and 1p loss in 19% of the evaluable cases. In our entire cohort, the median post-transplant follow-up was 36.5 months with a median progression free survival (PFS) of 24.8 months [95% confidence interval (CI): 18.4–31.3] and overall survival (OS) of 68.8 months (95% CI: 50.2–87.5). Patients with del(13q) and 1q21 gains had a significantly shorter PFS (median 15.8 vs. 33.4 months, p=0.002; median 19.1 vs. 33.4 months, p=0.011, respectively), and shorter OS (median 56.2 vs. 80.4 months, p=0.021; median 26.9 vs. 77.9 months, p=0.006, respectively), than those without such genetic abnormalities. In addition, 1p loss was associated with a significantly shorter PFS (median 18.2 vs. 37.9 months, p=0.001). However, there was no significant difference in PFS or OS in patients with or without the high-risk genetic factors t(4;14) or del(17p). On multivariate analysis adjusting for all 5 genetic risk factors, del(13q) was an independent prognostic factor for PFS (p=0.011) and OS (p=0.045).

Although LCO MM had a similar incidence of genetic abnormalities to common MM, only del(13q) and chromosome 1 abnormalities appear to adversely affect the survival in our cohort. Further larger, prospective studies are warranted to verify the role of these genomic aberrations in the genetic risk stratification of LCO MM.

Reece:Celgene: Honoraria, Research Funding.