Abstract

Bisphosphonates effectively reduce the number of skeletal-related events and relieve metastatic bone pain, improving quality of life in patients with malignant bone disease. However, clinical studies have highlighted that some, but not all intravenous (i.v.) bisphosphonates are associated with an increased risk of renal toxicity. The renal safety of bisphosphonates is particularly important in patients with multiple myeloma or in the elderly, who often have some degree of underlying renal damage and are at high risk of renal failure. In phase III trials, the renal safety profile of i.v. ibandronate was comparable to placebo. This agent may therefore be suitable for use in patients with impaired renal health. The current open-label study assessed the renal safety of ibandronate in elderly patients with multiple myeloma and varying stages of pre-existing renal impairment. Patients with multiple myeloma (creatinine clearance 8–139mL/min) received i.v. ibandronate (6mg, infused over 30 minutes). For each patient, deterioration in renal function was graded at baseline using creatinine clearance (grade 0: ≥80, 1: 50–79, 2: 30–49, 3: <30mL/min). Urinary markers of tubular damage (α-glutathione-S-transferase [α GST] and β-N-acetyl-glucosaminidase [βNAG]) were measured at baseline and at 24 and 72 hours following ibandronate infusion. Follow-up toxicity data was collected over 6 months for a subset of patients (n=6). A total of 29 patients (15 females and 14 males; mean age 71.1 ± 5 years) were included in this study. At baseline, four patients had a normal renal function (grade 0). The remaining 25 patients had varying degrees of renal insufficiency (grade 1: n=6, grade 2, n=8, grade 3: n=11). Mean proteinuria was 1799 ± 2140mg/24 hours. Serum creatinine and levels of urinary markers (α GST and βNAG) remained stable throughout the study. There was a statistically non-significant decrease in βNAG, and a positive correlation between ibandronate elimination and creatinine clearance. In the subset of six patients receiving six additional monthly infusions, ibandronate had no negative impact on renal function. To conclude, in this study of elderly patients with multiple myeloma, ibandronate was well tolerated and did not compromise renal health, despite 86% (25/29) of patients having pre-existing renal insufficiency. This was evidenced by markers of tubular damage and renal function, which remained unchanged throughout the study period. Furthermore, a subset of patients who received repeated ibandronate infusions did not experience renal toxicity. The management of drug-related nephrotoxicity needs special attention in patients with multiple myeloma, and in the elderly. These data suggest that ibandronate may be suitable for use in high risk multiple myeloma patients with pre-existing renal impairment. Further studies in larger groups of patients are warranted.

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