Pharmacokinetics and Safety of Elotuzumab in Combination with Lenalidomide and Dexamethasone in Patients with Multiple Myeloma and Various Levels of Renal Function: Results of a Phase 1b Study

• Type of Material: Conference Paper
• Authors: Jesus Berdeja, Sarah Cannon Research Institute; Sundar Jagannath, Mt. Sinai Medical Center; Jeffrey Zonder, Wayne State University; Ashraf Badros, University of Maryland; Jonathan Kaufman, Emory University; Robert Manges, Investigative Clinical Research of Indiana; Manish Gupta, Bristol Myers Squibb; Amol Tendolkar, Bristol Myers Squibb; Mark Lynch, Bristol Myers Squibb; Eric Bleickardt, Bristol Myers Squibb; Prashni Paliwal, Bristol Myers Squibb; Ravi Vij, Washington University in St. Louis
• Language: English
• Date: 2014-12-06
• Publisher: Emory University Libraries
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 The Authors.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.clml.2015.12.007
• Title of Journal or Parent Work: BLOOD
• Conference or Event Name: 56th Annual Meeting of the American-Society-of-Hematology
• Volume: 124
• Issue: 21
• Start Page: 129
• End Page: 138
• Grant/Funding Information: The present analysis was supported by research funding from Bristol-Myers Squibb. Writing and editorial assistance were provided by Sarah Addison, PhD, of Caudex, funded by Bristol-Myers Squibb.
• Keywords: Science & Technology; Life Sciences & Biomedicine; Hematology
• Research Categories: Health Sciences, Pharmacology; Chemistry, Pharmaceutical; Health Sciences, Medicine and Surgery

Abstract

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.