PMID- 28779463
OWN - NLM
STAT- MEDLINE
DCOM- 20190610
LR  - 20190613
IS  - 1179-1926 (Electronic)
IS  - 0312-5963 (Linking)
VI  - 57
IP  - 3
DP  - 2018 Mar
TI  - The Clinical Pharmacology of Elotuzumab.
PG  - 297-313
LID - 10.1007/s40262-017-0585-6 [doi]
AB  - Novel treatment options are needed to improve long-term outcomes for patients 
      with multiple myeloma (MM). In this article, we comprehensively review the 
      clinical pharmacology of elotuzumab, a first-in-class monoclonal anti-SLAMF7 
      antibody approved in combination with lenalidomide and dexamethasone (ELd) for 
      the treatment of patients with MM and one to three prior therapies. Elotuzumab 
      has a dual mechanism of action to specifically kill myeloma cells: binding SLAMF7 
      on myeloma cells facilitates natural killer (NK) cell-mediated antibody-dependent 
      cellular cytotoxicity (ADCC), and direct engagement of SLAMF7 on NK cells further 
      enhances NK cell activity. Elotuzumab administration causes transient elevations 
      of selected cytokines (tumor necrosis factor-alpha, interferon-gamma-induced protein-10 
      and monocyte chemoattractant protein-1). The temporary nature of these elevations 
      (greatest after the first dose, with a trend to return to baseline by day 7) 
      suggests a low likelihood of facilitating clinically meaningful drug-drug 
      interactions. Elotuzumab exposure increases more than proportionally to dose and 
      >80% SLAMF7 receptor occupancy is achieved with the approved elotuzumab 10 mg/kg 
      regimen. Population pharmacokinetic data from 375 patients demonstrated 
      weight-based dosing is appropriate for elotuzumab, and that ethnicity and 
      hepatic/renal function have minimal effects on exposure. Exposure-response 
      analysis of patients treated with ELd demonstrated that increased elotuzumab 
      exposure does not elevate the risk of grade 3+ adverse events (AEs) or AEs 
      leading to discontinuation/death. Elotuzumab antidrug antibodies occurred in 
      18.5% of patients treated with ELd or elotuzumab plus bortezomib and 
      dexamethasone, but were generally transient and did not affect elotuzumab 
      efficacy or safety. A monotherapy study indicated elotuzumab does not have 
      clinically relevant effects on QT intervals.
FAU - Passey, Chaitali
AU  - Passey C
AD  - Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, 3551 
      Lawrenceville Road, Princeton, NJ, 08540, USA.
FAU - Sheng, Jennifer
AU  - Sheng J
AD  - Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, 3551 
      Lawrenceville Road, Princeton, NJ, 08540, USA.
FAU - Mora, Johanna
AU  - Mora J
AD  - Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, 3551 
      Lawrenceville Road, Princeton, NJ, 08540, USA.
FAU - Tendolkar, Amol
AU  - Tendolkar A
AD  - Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, 3551 
      Lawrenceville Road, Princeton, NJ, 08540, USA.
FAU - Robbins, Michael
AU  - Robbins M
AD  - Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, 3551 
      Lawrenceville Road, Princeton, NJ, 08540, USA.
FAU - Dodge, Robert
AU  - Dodge R
AD  - Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, 3551 
      Lawrenceville Road, Princeton, NJ, 08540, USA.
FAU - Roy, Amit
AU  - Roy A
AD  - Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, 3551 
      Lawrenceville Road, Princeton, NJ, 08540, USA.
FAU - Bello, Akintunde
AU  - Bello A
AD  - Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, 3551 
      Lawrenceville Road, Princeton, NJ, 08540, USA.
FAU - Gupta, Manish
AU  - Gupta M
AD  - Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, 3551 
      Lawrenceville Road, Princeton, NJ, 08540, USA. Manish.Gupta-LVL@bms.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Switzerland
TA  - Clin Pharmacokinet
JT  - Clinical pharmacokinetics
JID - 7606849
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Cytokines)
RN  - 1351PE5UGS (elotuzumab)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - F0P408N6V4 (Lenalidomide)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal, Humanized/*administration & 
      dosage/pharmacokinetics/pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & 
      dosage/pharmacokinetics/pharmacology
MH  - Cytokines/metabolism
MH  - Dexamethasone/administration & dosage
MH  - Drug Interactions
MH  - Humans
MH  - Lenalidomide/administration & dosage
MH  - Multiple Myeloma/*drug therapy
EDAT- 2017/08/06 06:00
MHDA- 2019/06/14 06:00
CRDT- 2017/08/06 06:00
PHST- 2017/08/06 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2017/08/06 06:00 [entrez]
AID - 10.1007/s40262-017-0585-6 [pii]
AID - 10.1007/s40262-017-0585-6 [doi]
PST - ppublish
SO  - Clin Pharmacokinet. 2018 Mar;57(3):297-313. doi: 10.1007/s40262-017-0585-6.