Peripheral neuropathy outcomes and efficacy of subcutaneous bortezomib when combined with thalidomide and dexamethasone in the treatment of multiple myeloma.

Abstract

Due to the safety, convenience and efficacy of subcutaneous administration of bortezomib (scBor), it is becoming increasingly common to treat multiple myeloma (MM) using this treatment method. The current retrospective study suggested a lower incidence of peripheral neuropathy (PN) outcomes and superior efficacy following treatment with scBor combined with thalidomide and dexamethasone (VTD) in MM when compared with intravenous Bor (ivBor) treatment. The data of 81 patients from the Affiliated Hospital of Nantong University between September 2011 and February 2014 were analyzed, including 37 scBor and 44 ivBor patients administered a median (range) of 5.5 (3-8) and 6 (3-10) chemotherapy cycles, respectively. Adverse events (AEs) were assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for AEs, and response and progression were assessed by the International Myeloma Working Group criteria. Evidence of histopathology using transmission electron microscopy (TEM) was obtained from an in vivo model of adult Sprague Dawley (SD) rats. Following bortezomib-based VTD chemotherapy, patients had achieved very good partial remission or demonstrated no significant difference between the scBor and ivBor treatment groups (75.6 vs. 84.1%, respectively; P=0.350). The 1-year progression-free survival (83.8 vs. 84.1%, scBor vs. ivBor; P=0.921) and 1-year overall survival (OS) (91.9 vs. 90.9%, respectively; P=0.926) were also similar. PN rates of all the NCI grades were 51.3 and 61.3% (P=0.371); grade ≥2, 35.1 and 56.8% (P=0.052); and grade ≥3, 32.7 and 20.5% (P=0.015) in the subcutaneous and intravenous treatment groups, respectively, which suggests that severe PN may be less common following scBor treatment. There were no severe injection site reactions in the scBor-treated group. The incidence of adverse events were comparable between the two groups, including thrombocytopenia, anemia, fatigue and gastrointestinal symptoms such as nausea and vomiting. Furthermore, TEM images of the SD rat sciatic nerves revealed that all rats suffered PN to varying degrees, except the control group, and that the PN of ivBor-treated rats (in the presence and the absence of thalidomide) was more severe than that of scBor-treated rats. It was concluded that a subcutaneous dose of bortezomib of 1.3 mg/m2 may result in a lower incidence and severity of PN, with equivalent efficacy, as a component of combination VTD chemotherapy.