Phytohemagglutinin-induced IL2 mRNA in whole blood can predict bortezomib-induced peripheral neuropathy for multiple myeloma patients

The proteasome inhibitor bortezomib has revolutionized the treatment of multiple myeloma. However, bortezomib-induced peripheral neuropathy (BiPN) is a serious complication that compromises clinical outcome. If patients with a risk of developing BiPN could be predicted, physicians might prefer weekly, reduced-dose, or subcutaneous approaches. To seek biomarkers for BiPN, we conducted a multicenter prospective study using a simple and unique system. Multiple myeloma patients received twice-weekly or weekly 1.3 mg/m 2 bortezomib intravenously, and a 2-ml sample of whole blood was obtained before treatment and 2–3 days and 1–3 weeks after the first dose. Induction of gene expression was then quantified by real-time PCR. Of a total of 64 enrolled patients, 53 patient samples qualified for mRNA analysis. The BiPN grade was associated with phytohemagglutinin-induced IL2 , IFNG and TNFSF2 , as well as with lipopolysaccharide-induced IL6 levels. More importantly, of the 19 patients showing a ⩾3-fold increase in phytohemagglutinin-induced IL2 , 14 did not suffer from BiPN (73.7% prediction), whereas of the 34 patients with a