TY - JOUR
T1 - Pharmacokinetics and Safety of Elotuzumab Combined with Lenalidomide and Dexamethasone in Patients with Multiple Myeloma and Various Levels of Renal Impairment
T2 - Results of a Phase Ib Study
AU - Berdeja, Jesus
AU - Jagannath, Sundar
AU - Zonder, Jeffrey
AU - Badros, Ashraf
AU - Kaufman, Jonathan L.
AU - Manges, Robert
AU - Gupta, Manish
AU - Tendolkar, Amol
AU - Lynch, Mark
AU - Bleickardt, Eric
AU - Paliwal, Prashni
AU - Vij, Ravi
N1 - Funding Information:
Many thanks to all the patients, their families, and the investigators who participated in the present study. Elotuzumab was developed in a partnership between Bristol-Myers Squibb and AbbVie Biotherapeutics and is approved for use in combination with lenalidomide/dexamethasone in patients with multiple myeloma who have received one to three prior therapies. Bristol-Myers Squibb was involved in the study design; collection, analysis, and interpretation of data; and decision to submit the report for publication. 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 .
Publisher Copyright:
© 2016 The Authors.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - Creatinine clearance
KW - End-stage renal disease
KW - Glomerular filtration rate
KW - Monoclonal antibody
KW - SLAMF7
UR - http://www.scopus.com/inward/record.url?scp=84958940565&partnerID=8YFLogxK
U2 - 10.1016/j.clml.2015.12.007
DO - 10.1016/j.clml.2015.12.007
M3 - Article
C2 - 26795075
AN - SCOPUS:84958940565
SN - 2152-2650
VL - 16
SP - 129
EP - 138
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 3
ER -