Retrospective safety assessment of bendamustine in patients with renal impairment.

Abstract

e13081 Background: Patients with non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL) are at risk for renal impairment as the median age at diagnosis is >65 years. Bendamustine is a bifunctional alkylating agent with efficacy via several pathways and a manageable toxicity profile in NHL and CLL. There has been no published research on its safety in renally impaired NHL and CLL patients. Methods: In this retrospective study of 2 electronic medical record databases from US outpatient oncology practices, patients with NHL and CLL who had received ≥1 dose of bendamustine alone or with rituximab were identified and divided into investigator-defined subgroups: nonrenally impaired (creatinine clearance [CrCL] ≥40 or ≥60 mL/min) and renally impaired (CrCL <40 mL/min). Patients who received drugs with >5% risk of causing renal damage (eg, cisplatin, cyclosporine) were excluded. The study’s primary aim was to evaluate laboratory toxicities in the NHL and CLL groups. Results: Of 379 CLL patients, 42 had CrCL <40, 144 had CrCL ≥40-60, and 193 CrCL ≥60 mL/min; of 561 NHL patients, 62 had CrCL <40, 153 had CrCL ≥40-60, and 346 had CrCL ≥60 mL/min. Baseline characteristics were similar, except for more advanced age, shorter mean disease duration, and a slightly lower initial bendamustine dose in renally impaired patients. Mean total bendamustine exposure was 12 weeks for renally impaired vs 15 weeks for nonrenally impaired CLL patients, and ~16 weeks for both NHL groups. No statistically significant differences in laboratory toxicities were seen among the CLL groups, but renally impaired NHL patients had an increased risk for grade 3/4 thrombocytopenia (Cox hazard ratio [HR]: 2.57; 95% CI: 1.13, 5.85) vs those with CrCL ≥60 mL/min. In combined CLL and NHL groups, only grade 3/4 BUN increase was significantly higher for renally impaired patients vs those with CrCL ≥40 mL/min (HR: 2.36; 95% CI: 1.15, 4.86) or ≥60 mL/min (HR: 4.46; 95% CI: 1.79, 11.14). Conclusions: Though sample size and time of exposure limit the power of this study, the results support the safety of bendamustine in renally impaired NHL and CLL patients. Monitoring blood counts and renal function is probably prudent. Support: Teva Pharmaceutical Industries Ltd., Frazer, PA.