title: 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: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  The results of the present study support the use of elotuzumab for the treatment of patients with MM and renal dysfunction without dose adjustment.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN. Electronic address: jberdeja@tnonc.com.
authors.forename: Jesus
authors.initials: J
authors.lastname: Berdeja
authors.affiliation: Mount Sinai Hospital, New York, NY.
authors.forename: Sundar
authors.initials: S
authors.lastname: Jagannath
authors.affiliation: Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Zonder
authors.affiliation: University of Maryland, Baltimore, MD.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Badros
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Kaufman
authors.affiliation: Investigative Clinical Research of Indiana, Indianapolis, IN.
authors.forename: Robert
authors.initials: R
authors.lastname: Manges
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Manish
authors.initials: M
authors.lastname: Gupta
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Amol
authors.initials: A
authors.lastname: Tendolkar
authors.affiliation: Bristol-Myers Squibb, Wallingford, CT.
authors.forename: Mark
authors.initials: M
authors.lastname: Lynch
authors.affiliation: Bristol-Myers Squibb, Wallingford, CT.
authors.forename: Eric
authors.initials: E
authors.lastname: Bleickardt
authors.affiliation: Bristol-Myers Squibb, Wallingford, CT.
authors.forename: Prashni
authors.initials: P
authors.lastname: Paliwal
authors.affiliation: Division of Hematology and Oncology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Ravi
authors.initials: R
authors.lastname: Vij
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D020732:Cytogenetic Analysis; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D007677:Kidney Function Tests; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D009367:Neoplasm Staging; D019233:Retreatment; D012720:Severity of Illness Index; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C546027:elotuzumab; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide
keywords: Creatinine clearance; End-stage renal disease; Glomerular filtration rate; Monoclonal antibody; SLAMF7