Pharmacokinetics and Safety of Elotuzumab Combined With Lenalidomide and Dexamethasone in Patients With Multiple Myeloma and Various Levels of Renal Impairment: Results of a Phase Ib Study.

Abstract

Renal impairment is associated with a poor prognosis in patients with multiple myeloma (MM), and more treatment options are needed. The pharmacokinetics of elotuzumab, a humanized IgG1 monoclonal antibody, combined with lenalidomide and dexamethasone, is not significantly different between patients with MM with and without renal impairment, suggesting that elotuzumab might be administered without dose adjustment for renal function.Introduction:The present study evaluated the pharmacokinetics and safety of elotuzumab, a humanized IgG1 monoclonal antibody against signaling lymphocyte activation molecule-F7, combined with lenalidomide and dexamethasone, in patients with multiple myeloma (MM) and renal impairment.Patients and Methods:Patients with MM and normal renal function (NRF) (creatinine clearance [CrCl] ≥ 90 mL/min), severe renal impairment (SRI) (CrCl < 30 mL/min, not requiring dialysis), or end-stage renal disease (ESRD) (requiring dialysis) were enrolled in this open-label, phase Ib study. Elotuzumab (10 mg/kg), lenalidomide (5–25 mg), and dexamethasone (40 mg) were administered in 28-day cycles until disease progression or unacceptable toxicity developed. The primary endpoint was single-dose elotuzumab pharmacokinetics.Results:A total of 26 patients (median age, 63 years) were treated (NRF, n = 8; SRI, n = 9; ESRD, n = 9). The median baseline CrCl was 105 mL/min (range, 84–146 mL/min) for those with NRF and 26 mL/min (range, 15–33 mL/min) for those with SRI. Twenty-three patients (89%) had received previous therapy (median, 2 regimens; range, 1–7). Treatment was discontinued in 6 patients with NRF, 4 with SRI, and 5 with ESRD, primarily because of disease progression. The mean elotuzumab serum concentrations were comparable across groups (n = 23). No statistically significant differences were observed in the maximum observed serum concentration, area under the concentration–time curve from time 0 to the last quantifiable serum concentration, or area under the concentration–time curve from time 0 to infinity when the SRI and ESRD groups were compared with the NRF group (P >.05). All patients had > 1 adverse event (AE). Of the 8 patients with NRF, 9 with SRI, and 9 with ESRD, 7,8, and 7 experienced grade 3 to 4 AEs. The overall response rates were 75% in the NRF, 67% in the SRI, and 56% in the ESRD groups.Conclusion:The results of the present study support the use of elotuzumab for the treatment of patients with MM and renal dysfunction without dose adjustment.