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

Clin Lymphoma Myeloma Leuk. 2016 Mar;16(3):129-38. doi: 10.1016/j.clml.2015.12.007. Epub 2015 Dec 21.


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.

Keywords: Creatinine clearance; End-stage renal disease; Glomerular filtration rate; Monoclonal antibody; SLAMF7.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cytogenetic Analysis
  • Dexamethasone / administration & dosage
  • Dexamethasone / pharmacokinetics
  • Female
  • Humans
  • Kidney Diseases / complications*
  • Kidney Diseases / diagnosis
  • Kidney Diseases / physiopathology
  • Kidney Function Tests
  • Lenalidomide
  • Male
  • Middle Aged
  • Multiple Myeloma / complications*
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Neoplasm Staging
  • Retreatment
  • Severity of Illness Index
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives
  • Thalidomide / pharmacokinetics
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • elotuzumab
  • Thalidomide
  • Dexamethasone
  • Lenalidomide