PMID- 22291084
OWN - NLM
STAT- MEDLINE
DCOM- 20120730
LR  - 20220310
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 30
IP  - 16
DP  - 2012 Jun 1
TI  - Phase I trial of anti-CS1 monoclonal antibody elotuzumab in combination with 
      bortezomib in the treatment of relapsed/refractory multiple myeloma.
PG  - 1960-5
LID - 10.1200/JCO.2011.37.7069 [doi]
AB  - PURPOSE: 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). PATIENTS AND 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. CONCLUSION: The 
      combination of elotuzumab and bortezomib was generally well-tolerated and showed 
      encouraging activity in patients with relapsed/refractory MM.
FAU - Jakubowiak, Andrzej J
AU  - Jakubowiak AJ
AD  - University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA. 
      ajakubowiak@medicine.bsd.uchicago.edu
FAU - Benson, Don M
AU  - Benson DM
FAU - Bensinger, William
AU  - Bensinger W
FAU - Siegel, David S D
AU  - Siegel DS
FAU - Zimmerman, Todd M
AU  - Zimmerman TM
FAU - Mohrbacher, Ann
AU  - Mohrbacher A
FAU - Richardson, Paul G
AU  - Richardson PG
FAU - Afar, Daniel E H
AU  - Afar DE
FAU - Singhal, Anil K
AU  - Singhal AK
FAU - Anderson, Kenneth C
AU  - Anderson KC
LA  - eng
GR  - P01 CA078378/CA/NCI NIH HHS/United States
GR  - P01 CA155258/CA/NCI NIH HHS/United States
GR  - P50 CA100707/CA/NCI NIH HHS/United States
GR  - R01 CA050947/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20120130
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Boronic Acids)
RN  - 0 (Pyrazines)
RN  - 1351PE5UGS (elotuzumab)
RN  - 69G8BD63PP (Bortezomib)
SB  - IM
CIN - J Clin Oncol. 2012 Jun 1;30(16):1904-6. PMID: 22291081
CIN - J Clin Oncol. 2012 Jun 1;30(16):1974-9. PMID: 22508813
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Boronic Acids/*administration & dosage
MH  - Bortezomib
MH  - Female
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy
MH  - Pyrazines/*administration & dosage
MH  - Recurrence
PMC - PMC4874204
COIS- Authors' disclosures of potential conflicts of interest and author contributions 
      are found at the end of this article.
EDAT- 2012/02/01 06:00
MHDA- 2012/07/31 06:00
PMCR- 2012/01/30
CRDT- 2012/02/01 06:00
PHST- 2012/02/01 06:00 [entrez]
PHST- 2012/02/01 06:00 [pubmed]
PHST- 2012/07/31 06:00 [medline]
PHST- 2012/01/30 00:00 [pmc-release]
AID - JCO.2011.37.7069 [pii]
AID - 77069 [pii]
AID - 10.1200/JCO.2011.37.7069 [doi]
PST - ppublish
SO  - J Clin Oncol. 2012 Jun 1;30(16):1960-5. doi: 10.1200/JCO.2011.37.7069. Epub 2012 
      Jan 30.