Impact on response and survival of DNA repair single nucleotide polymorphisms in relapsed or refractory multiple myeloma patients treated with thalidomide.

Single nucleotide polymorphisms (SNPs) in 12 genes involving multidrug resistance, drug metabolic pathways, DNA repair systems and cytokines were examined in 28 patients with relapsed/refractory multiple myeloma (MM) treated with single agent thalidomide and the results were correlated with response, toxicity and overall survival (OS). The response rate was higher in patients with SNPs in ERCC1 (rs735482) (p=0.006), ERCC5 (rs17655) (p=0.04) or XRCC5 (rs1051685) (p=0.013). Longer OS was associated with the SNP in ERCC1 (rs735482) (p=0.005) and XRCC5 (rs1051685) (p=0.02). Finally, polymorphism in GSTT1 (rs4630) was associated with a lower frequency of thalidomide-induced peripheral neuropathy (p=0.04).