PMID- 23670297
OWN - NLM
STAT- MEDLINE
DCOM- 20140310
LR  - 20211021
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 27
IP  - 12
DP  - 2013 Dec
TI  - Treatment outcomes in patients with relapsed and refractory multiple myeloma and 
      high-risk cytogenetics receiving single-agent carfilzomib in the PX-171-003-A1 
      study.
PG  - 2351-6
LID - 10.1038/leu.2013.152 [doi]
AB  - Several cytogenetic abnormalities are associated with poor outcomes in multiple 
      myeloma (MM). We prospectively analyzed the impact of cytogenetic abnormalities 
      on outcomes during the phase 2 PX-171-003-A1 study of single-agent carfilzomib 
      for relapsed and refractory MM. In the response-evaluable population (257/266), 
      fluorescence in situ hybridization (FISH)/conventional cytogenetic profiles were 
      available for 229 patients; 62 (27.1%) had high-risk cytogenetics--del 17p13, 
      t(4;14) or t(14;16) by interphase FISH or deletion 13 or hypodiploidy by 
      metaphase cytogenetics--and 167 (72.9%) had standard-risk profiles. Generally, 
      baseline characteristics were similar between the subgroups, but International 
      Staging System stage III disease was more common in high- vs standard-risk 
      patients (41.9% vs 27.5%) as was Eastern Cooperative Oncology Group performance 
      status 1/2 (85.5% vs 68.3%). Overall response was comparable between the 
      subgroups (25.8% vs 24.6%, respectively; P=0.85), while time-to-event end points 
      showed a trend of shorter duration in high-risk patients, including median 
      duration of response (5.6 months (95% confidence interval (CI) 3.7-7.8) vs 8.3 
      months (95% CI 5.6-12.3)) and overall survival (9.3 (95% CI 6.5-13.0) vs 19.0 
      months (95% CI 15.4-NE); P=0.0003). Taken together, these findings demonstrate 
      that single-agent carfilzomib is efficacious and has the potential to at least 
      partially overcome the impact of high-risk cytogenetics in heavily pre-treated 
      patients with MM.
FAU - Jakubowiak, A J
AU  - Jakubowiak AJ
AD  - Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, 
      IL, USA.
FAU - Siegel, D S
AU  - Siegel DS
FAU - Martin, T
AU  - Martin T
FAU - Wang, M
AU  - Wang M
FAU - Vij, R
AU  - Vij R
FAU - Lonial, S
AU  - Lonial S
FAU - Trudel, S
AU  - Trudel S
FAU - Kukreti, V
AU  - Kukreti V
FAU - Bahlis, N
AU  - Bahlis N
FAU - Alsina, M
AU  - Alsina M
FAU - Chanan-Khan, A
AU  - Chanan-Khan A
FAU - Buadi, F
AU  - Buadi F
FAU - Reu, F J
AU  - Reu FJ
FAU - Somlo, G
AU  - Somlo G
FAU - Zonder, J
AU  - Zonder J
FAU - Song, K
AU  - Song K
FAU - Stewart, A K
AU  - Stewart AK
FAU - Stadtmauer, E
AU  - Stadtmauer E
FAU - Harrison, B L
AU  - Harrison BL
FAU - Wong, A F
AU  - Wong AF
FAU - Orlowski, R Z
AU  - Orlowski RZ
FAU - Jagannath, S
AU  - Jagannath S
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - P50 CA142509/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20130514
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Oligopeptides)
RN  - 72X6E3J5AR (carfilzomib)
SB  - IM
CIN - Leukemia. 2013 Dec;27(12):2269-71. PMID: 24326595
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*therapeutic use
MH  - *Chromosome Aberrations
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy/genetics
MH  - Oligopeptides/*therapeutic use
MH  - Survival Analysis
MH  - Treatment Outcome
PMC - PMC3865533
EDAT- 2013/05/15 06:00
MHDA- 2014/03/13 06:00
CRDT- 2013/05/15 06:00
PHST- 2013/02/07 00:00 [received]
PHST- 2013/04/12 00:00 [revised]
PHST- 2013/04/24 00:00 [accepted]
PHST- 2013/05/15 06:00 [entrez]
PHST- 2013/05/15 06:00 [pubmed]
PHST- 2014/03/13 06:00 [medline]
AID - leu2013152 [pii]
AID - 10.1038/leu.2013.152 [doi]
PST - ppublish
SO  - Leukemia. 2013 Dec;27(12):2351-6. doi: 10.1038/leu.2013.152. Epub 2013 May 14.