Impact of Cytogenetic Abnormalities On Outcome Among Patients with Relapsed/Refractory Multiple Myeloma Treated with Bortezomib: Adverse Effect of 1q21 (CKS1B) Amplification.

Abstract 2826

Poster Board II-802

To investigate whether genetic risk factors affect the outcome of relapsed/refractory myeloma patients undergoing bortezomib therapy, we evaluated the clinical features of 85 patients treated with bortezomib and correlated with the high-risk cytogenetic abnormalities as detected by interphase cytoplasmic fluorescence in situ hybridization (cIg-FISH). Forty (47%) patients had an objective response to bortezomib with median progression free (PFS) and overall survivals (OS) of 9.4 and 12.6 months, respectively. cIg-FISH determination of del(13q), del(17p), del(1p21), t(4;14), and amp. (1q21)(CKS1B) was done on 79, 77, 77, 78, and 80 cases and the frequency of their detection was 38%, 22%, 26%, 18%, and 39%, respectively. There was no statistically significant difference in terms of response or duration of response to bortezomib for patients with or without any of the cytogenetic abnormalities. PFS was also comparable among patients with and without the aforementioned genetic markers. However, patients with 1q21(CKS1B) amplification had significantly shorter OS than those without such abnormality (5.3 vs. 24.6 months, p=0.0005). Multi-variate analysis adjusting for all 5 high-risk genetic factors confirmed that 1q21(CKS1B) amplification is an independent risk factor for OS (p=0.008). Improved therapeutic strategies may be required for this subgroup of patients.