Renal safety of zoledronic acid with thalidomide in patients with myeloma: a pharmacokinetic and safety sub-study

Twenty-four patients who were enrolled in a large randomized trial of thalidomide vs no thalidomide maintenance therapy for myeloma, in which all patients also received zoledronic acid, were recruited to a pharmacokinetic and renal safety sub-study, and followed for up to 16 months.No significant differences by Wilcoxon rank-sum statistic were found in zoledronic acid pharmacokinetics or renal safety for up to 16 months in patients randomized to thalidomide or not.In myeloma patients receiving maintenance therapy, the combination of zoledronic acid and thalidomide appears to confer no additional renal safety risks over zoledronic acid alone.Modern therapy of multiple myeloma (MM) combines treatments to induce disease response (e.g. thalidomide, corticosteroids and cytotoxic agents) with supportive care to prevent bone and infective complications (e.g. bisphosphonates and antibiotics). However, combining agents might cause interactions that increase toxicity or lessen efficacy. Case reports suggested that MM patients receiving zoledronic acid combined with thalidomide had higher risks of renal impairment [1]. Hence, the United States' Food and Drug Administration requested that Novartis (manufacturer of zoledronic acid) conduct a study to look for pharmacokinetic interaction between zoledronic acid and thalidomide, and to monitor renal safety of MM patients receiving both drugs.The Australasian Leukaemia and Lymphoma Group (ALLG) was conducting a large (>200 patients), randomized clinical trial (ALLG MM6) in MM patients, who had received high-dose therapy and autologous stem cell transplantation (ASCT), to ascertain the efficacy and safety of thalidomide and prednisolone maintenance therapy compared to prednisolone maintenance therapy post-transplantation. All patients were scheduled to receive adjunctive zoledronic acid intravenously on a 4th-weekly basis. The ALLG agreed to incorporate a safety sub-study into the ALLG MM6 study to assess the pharmacokinetics of zol