Renal impairment in multiple myeloma patients following zoledronic acid or ibandronate treatment

Abstract

17501 Background: Although bisphosphonates prevent skeletal complications, agents differ with respect to renal safety. Ibandronate (IB) is a single-nitrogen, noncyclic bisphosphonate that has shown a renal safety profile comparable to placebo in phase III trials. This retrospective study aimed to compare renal impairment rates in multiple myeloma (MM) patients treated with IB or zoledronic acid (ZO). Methods: Medical records in a German oncology clinic (Praxisklinik für Hämatologie und Onkologie Koblenz, Koblenz, Germany) from May 2001 to December 2005 were retrospectively reviewed. Creatinine measurements were analyzed from baseline (before ZO or IB treatment) to last evaluation for each patient. Renal impairment was defined as (1) a serum creatinine (SCr) increase of ≥0.5 mg/dL or ≥1.0 mg/dL from baseline values of <1.4 mg/dL or ≥1.4 mg/dL, respectively, or (2) a ≥25% decrease in glomerular filtration rate (GFR; abbreviated MDRD formula) from baseline. Patients treated sequentially with both ZO and IB were included as separate observations. Andersen-Gill extension of the Cox model was used for multiple-event analysis. Results: In 84 MM patients, 69 received ZO and 40 received IB, with 25 patients receiving both drugs. Compared with IB, the ZO group had a significantly better baseline renal function (mean SCr 1.01 vs 1.34, p = 0.007; mean GFR 75.9 vs 57.3, p = 0.0002). Data analysis showed that ZO treatment increased the relative risk (RR) of renal impairment by ∼3-fold compared with IB (renal impairment rates: ZO 39.1% vs IB 10.8%, RR = 3.6, p = 0.002 [SCr]; 62.3% vs 24.3%, RR = 2.6, p = 0.0002 [GFR]). The incidence rate of renal impairment was higher for ZO than IB (SCr: 1.14 vs 0.48 events per person-year, p = 0.169; GFR: 2.65 vs 0.87 events per person-year, p = 0.007). Multiple-event analysis found significantly higher hazards ratios for ZO over IB (SCr = 5.3; GFR = 2.7; both p < 0.0001). Conclusions: In this retrospective review, MM patients were significantly more likely to experience renal impairment with ZO than with IB. A prospective randomized study is warranted for further validation. [Table: see text]