title: Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma.
abstract: OBJECTIVE
  This phase I study evaluated elotuzumab, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma (MM).
  
  
  METHODS
  Three cohorts were enrolled and treated with elotuzumab (5.0, 10, or 20 mg/kg intravenously) on days 1, 8, 15, and 22 of a 28-day cycle in the first two cycles, and days 1 and 15 of each subsequent cycle; lenalidomide 25 mg orally [PO] on days 1 to 21; and dexamethasone 40 mg PO weekly. Dose-limiting toxicities (DLTs) were assessed during cycle 1 of each cohort, and clinical responses were evaluated during each cycle. The first five patients received up to six cycles of therapy; subsequent patients were treated until disease progression.
  
  
  RESULTS
  Twenty-nine patients with advanced MM and a median of three prior MM therapies were enrolled; 28 patients were treated, three each in the 5.0-mg/kg and 10-mg/kg cohorts and 22 in the 20-mg/kg cohort. No DLTs were observed up to the maximum proposed dose of 20 mg/kg. The most frequent grade 3 to 4 toxicities were neutropenia (36%) and thrombocytopenia (21%). Two patients experienced a serious infusion reaction (one grade 4 anaphylactic reaction and one grade 3 stridor) during the first treatment cycle. Objective responses were obtained in 82% (23 of 28) of treated patients. After a median of 16.4 months follow-up, the median time to progression was not reached for patients in the 20-mg/kg cohort who were treated until disease progression.
  
  
  CONCLUSIONS
  The combination of elotuzumab, lenalidomide, and low-dose dexamethasone was generally well tolerated and showed encouraging response rates in patients with relapsed or refractory MM.
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, USA. sloni01@emory.edu
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.forename: Ravi
authors.initials: R
authors.lastname: Vij
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Amitabha
authors.initials: A
authors.lastname: Mazumder
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Kaufman
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.forename: L Claire
authors.initials: LC
authors.lastname: Tsao
authors.forename: Christopher
authors.initials: C
authors.lastname: Westland
authors.forename: Anil K
authors.initials: AK
authors.lastname: Singhal
authors.forename: Sundar
authors.initials: S
authors.lastname: Jagannath
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage; D018450:Disease Progression; D004334:Drug Administration Schedule; D006801:Humans; D000077269:Lenalidomide; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D012008:Recurrence; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C546027:elotuzumab; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide