Analysis of High-Risk Genomic Aberrations in Light Chain Only Multiple Myeloma
C Qi, Y Trieu, W Xu, D Reece, H Chang. University Health Network, University of Toronto, Toronto, Canada
Background: Multiple myeloma (MM) is characterized by an expansion of clonal plasma cells with production of monoclonal immunoglobulin. Majority of MM patients have intact immunoglobulin, but in a subset of patients (∼15%), their tumors produce 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.
Design: We investigated a cohort of 53 LCO MM cases diagnosed at our institution. All patients received high dose therapy with stem cell support, their free light chains were detected by a sensitive free light chain assay that allows a nephelometric measurement of free kappa and lambda light chains that circulate as monomers or dimmers. The genomic risk factors including del(13q), del(17p) and t(4;14) were evaluated by cytoplasmic fluorescence in situ hybridization (cIg-FISH) and correlated with their clinical outcomes.
Results: There were 32 males and 21 females with a median age of 56, 37 had free kappa, 16 free lambda light chains; 12 were classified as ISS stage III, 10 stage II and 31 stage I disease. Del(13q), del(p17p) and t(4;14) were detected in 41%, 23% and 15%, respectively. Of 39 patients with the status of all 3 genetic factors available, 3 had coexistence of 3 abnormalities, 5 had 2 and 12 had 1 only. The median overall survival (OS) in this cohort was not reached with a 3-year OS rate of 81%, the median progression free survival (PFS) was 21.1 months (95% CI: 17.6-29.8). There was no significant difference in PFS or OS in patients with or without any of the genetic abnormalities tested. When patients with either del(17p) or t(4;14) were classified as a high-risk group, the PFS (P= 0.36) or OS (P=0.39) were compatible with the group without del(17) or t(4;14).
Conclusions: To our knowledge, this is the first report to systematically analyze the impact of high-risk genetic factors on the outcome of LCO MM patients. Although MM –associated genetic changes were detected with similar incidence to other MMs, they appear not affect the survivals in our cohort, thus, may not be applicable to the genetic risk stratification in LCO MM. Larger prospective studies are required to confirm our observation and to further identify genetic factors that can predict the clinical outcomes in this subgroup of MM patients.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 205, Tuesday Morning