Renal toxicity associated with zoledronic acid and pamidronate in multiple myeloma patients: A retrospective study

Abstract

17515 Background: Patients (pts) with multiple myeloma (MM) are at an increased risk of renal impairment as part of disease progression. Herein we compared rates of renal toxicity in MM pts treated with zoledronic acid (ZO), pamidronate (PA), and no bisphosphonate (BP) treatment (NT). Methods: Medical and pharmacy claims and laboratory data were reviewed from >35 managed care plans between 01/2000 and 12/2004. Inclusion criteria were ≥2 claims for MM, no gap in health coverage, and serum creatinine readings before and after first ZO or PA infusion. MM pts who received NT served as a separate reference group. Observation periods extended from initial BP infusion to health plan disenrollment (BP monotherapy) or BP switch. Renal impairment was defined as a ≥25% decrease in glomerular filtration rate (GFR,abbreviated MDRD formula) from baseline. Andersen-Gill model, adjusted for demographics and baseline comorbidities, was used to analyze multiple events in a given pt, as physician practice patterns indicate that administration of both BPs continues even after the development of a first renal event. Results: The study population comprised 122 ZO-treated pts, 90 PA-treated pts, and 213 NT pts. Baseline characteristics of ZO and PA groups were similar except the ZO group had a significantly better baseline GFR and higher previous nephrotoxic drug use (both p < 0.01). After treatment, ZO and PA groups had similar renal impairment rates that were significantly higher than the NT group and increased with treatment duration (ZO 21.7%, PA 22.9%, NT 17.0% in pts treated for <6 months; increasing to ZO 53.8%, PA 50.0%, NT 33.7% in pts treated for ≥18 months). Mean renal impairment events per person-year were significantly higher for ZO than PA (1.83 vs 0.78, p < 0.001). Multiple-event analysis found a 2.6 times risk of renal impairment for ZO than PA (p < 0.0001). Compared with PA, ZO-treated pts had a steeper decrease in mean GFR from baseline by 8.5% (p = 0.03). Conclusions: This retrospective observational study suggests that in MM patients, both ZO and PA are associated with a similar higher risk of renal impairment than NT, but ZO-treated pts are significantly more likely to experience multiple impairment events upon repeated administrations. [Table: see text]