Bortezomib pharmacokinetics in tumor response and peripheral neuropathy in multiple myeloma patients receiving bortezomib-containing therapy.

The usefulness of pharmacokinetics of bortezomib for multiple myeloma (MM) with respect to the maximum response to bortezomib and bortezomib-induced peripheral neuropathy (BIPN) development was studied. Maximum response to subcutaneous bortezomib therapy and BIPN occurrence for the first 12 weeks of treatment in 35 MM patients treated by bortezomib-dexamethasone (VD) and bortezomib-melphalan-prednisone (VMP) were evaluated. On day 1 of cycle 1, seven whole-blood samples were collected for 3 h after dosing completion to obtain the maximum plasma concentration and area under the time-concentration curve during 3 h postdose (AUC0-3) in each patient. A total of 35 patients with complete data were analyzed and the overall response rate was 91.4%. Complete response (CR) was observed in 42.9% patients. The maximum plasma concentration (Cmax) was significant for the CR rate in two different models [full model: odds ratio (OR)=1.092; P=0.038, final model: OR=1.081; P=0.038]. In addition, Cmax was associated with a progression-free survival advantage. Overall, 48.6% of patients developed BIPN including peripheral sensory neuropathy and neuralgia. The VMP-treated patients had a higher risk compared with the VD-treated patients (OR=21.662; P=0.029). Cmax had a tendency to affect the occurrence of BIPN (≥grade 2) (OR=1.064; P=0.092). In real-world clinical practice using bortezomib for MM patients, Cmax among pharmacokinetic factors significantly affected the achievement of CR. The VMP-treated patients showed vulnerability to BIPN, suggesting the necessity for more careful monitoring.