Impact of cytogenetics in patients with relapsed or refractory multiple myeloma treated with bortezomib: Adverse effect of 1q21 gains.

We investigated the influence of genetic risk factors on the clinical response to bortezomib in 85 relapsed/refractory multiple myeloma (MM) patients. Interphase cytoplasmic fluorescence in situ hybridization (cIg-FISH) detected del(13q), del(17p), del(1p21), t(4;14), and 1q21 gain in 38%, 22%, 26%, 18% and 39% of evaluable cases. Forty-nine patients (49%) responded to bortezomib with median progression free (PFS) and overall survivals (OS) of 5.0 and 12.6 months, respectively. Patients with 1q21 gain had a significantly shorter OS (5.3 months vs. 24.6 months, p=0.0006) and PFS (2.3 months vs. 7.3 months, p=0.003) than patients without such abnormality. There was no significant difference in response rate, response duration, PFS or OS for any of the other genetic risk factors tested. Multivariate analysis confirmed that 1q21 gain is an independent risk factor for PFS (p=0.03) and OS (p=0.009) of bortezomib-treated relapsed/refractory myeloma.