title: Phase I trial of anti-CS1 monoclonal antibody elotuzumab in combination with bortezomib in the treatment of relapsed/refractory multiple myeloma.
abstract: OBJECTIVE
  To evaluate the maximum-tolerated dose (MTD), safety, and efficacy of elotuzumab in combination with bortezomib in patients with relapsed or relapsed and refractory multiple myeloma (MM).
  
  
  METHODS
  Elotuzumab (2.5, 5.0, 10, or 20 mg/kg intravenously [IV]) and bortezomib (1.3 mg/m(2) IV) were administered on days 1 and 11 and days 1, 4, 8, and 11, respectively, in 21-day cycles by using a 3 + 3 dose-escalation design. Patients with stable disease or better after four cycles could continue treatment until disease progression or unexpected toxicity. Responses were assessed during each cycle by using European Group for Blood and Marrow Transplantation (EBMT) criteria.
  
  
  RESULTS
  Twenty-eight patients with a median of two prior therapies were enrolled; three patients each received 2.5, 5.0, and 10 mg/kg of elotuzumab and 19 received 20 mg/kg (six during dose escalation and 13 during an expansion phase). No dose-limiting toxicities were observed during cycle 1 of the dose-escalation phase, and the MTD was not reached up to the maximum planned dose of 20 mg/kg. The most frequent grade 3 to 4 adverse events (AEs) were lymphopenia (25%) and fatigue (14%). Two elotuzumab-related serious AEs of chest pain and gastroenteritis occurred in one patient. An objective response (a partial response or better) was observed in 13 (48%) of 27 evaluable patients and in two (67%) of three patients refractory to bortezomib. Median time to progression was 9.46 months.
  
  
  CONCLUSIONS
  The combination of elotuzumab and bortezomib was generally well-tolerated and showed encouraging activity in patients with relapsed/refractory MM.
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA. ajakubowiak@medicine.bsd.uchicago.edu
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Jakubowiak
authors.forename: Don M
authors.initials: DM
authors.lastname: Benson
authors.forename: William
authors.initials: W
authors.lastname: Bensinger
authors.forename: David S D
authors.initials: DS
authors.lastname: Siegel
authors.forename: Todd M
authors.initials: TM
authors.lastname: Zimmerman
authors.forename: Ann
authors.initials: A
authors.lastname: Mohrbacher
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Daniel E H
authors.initials: DE
authors.lastname: Afar
authors.forename: Anil K
authors.initials: AK
authors.lastname: Singhal
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011719:Pyrazines / Q000008:administration & dosage*; D012008:Recurrence
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D001897:Boronic Acids; D011719:Pyrazines; C546027:elotuzumab; D000069286:Bortezomib