PMID- 26193999
OWN - NLM
STAT- MEDLINE
DCOM- 20160106
LR  - 20211203
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 121
IP  - 20
DP  - 2015 Oct 15
TI  - Complex karyotype is a stronger predictor than del(17p) for an inferior outcome 
      in relapsed or refractory chronic lymphocytic leukemia patients treated with 
      ibrutinib-based regimens.
PG  - 3612-21
LID - 10.1002/cncr.29566 [doi]
AB  - BACKGROUND: Ibrutinib is active in patients with relapsed/refractory (R/R) 
      chronic lymphocytic leukemia (CLL). In patients treated with ibrutinib for R/R 
      CLL, del(17p), identified by interphase fluorescence in situ hybridization 
      (FISH), is associated with inferior progression-free survival despite equivalent 
      initial response rates. Del(17p) is frequently associated with a complex 
      metaphase karyotype (CKT); the prognostic significance of CKT in 
      ibrutinib-treated patients has not been reported. METHODS: This study reviewed 88 
      patients treated for R/R CLL at The University of Texas MD Anderson Cancer Center 
      with investigational ibrutinib-based regimens from 2010 to 2013. Pretreatment 
      FISH and lipopolysaccharide-stimulated metaphase cytogenetic analysis were 
      performed on bone marrow. RESULTS: An adequate pretreatment metaphase karyotype 
      was available for 56 of the 88 patients. The karyotype was complex in 21 of the 
      56 cases; 17 of the 21 had del(17p) according to FISH. The overall response rate, 
      including partial remission with persistent lymphocytosis, was 94%; 18% had 
      complete responses. In a multivariate analysis (MVA), only CKT was significantly 
      associated with event-free survival (EFS; hazard ratio [HR], 6.6 [95% CI 
      1.7-25.6]; P = .006). Fludarabine-refractory CLL (HR, 6.9 [95% CI 1.8-27.1], 
      P = .005) and CKT (HR 5.9 [95% CI 1.6-22.2], P = .008) were independently 
      associated with inferior overall survival (OS) in MVA. Del(17p) by FISH was not 
      significantly associated with EFS or OS in MVA. CONCLUSIONS: CKT is a powerful 
      predictor of outcomes for ibrutinib-treated patients with R/R CLL and may be a 
      stronger predictor of biological behavior than del(17p) by FISH. Because of their 
      relatively poor outcomes, patients with CKT are ideal candidates for studies of 
      consolidative treatment strategies or novel treatment combinations.
CI  - (c) 2015 American Cancer Society.
FAU - Thompson, Philip A
AU  - Thompson PA
AD  - Department of Leukemia, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - O'Brien, Susan M
AU  - O'Brien SM
AD  - Department of Leukemia, University of California, Irvine, California.
FAU - Wierda, William G
AU  - Wierda WG
AD  - Department of Leukemia, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Ferrajoli, Alessandra
AU  - Ferrajoli A
AD  - Department of Leukemia, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Stingo, Francesco
AU  - Stingo F
AD  - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Smith, Susan C
AU  - Smith SC
AD  - Department of Leukemia, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Burger, Jan A
AU  - Burger JA
AD  - Department of Leukemia, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Estrov, Zeev
AU  - Estrov Z
AD  - Department of Leukemia, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Jain, Nitin
AU  - Jain N
AD  - Department of Leukemia, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Kantarjian, Hagop M
AU  - Kantarjian HM
AD  - Department of Leukemia, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Keating, Michael J
AU  - Keating MJ
AD  - Department of Leukemia, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
LA  - eng
GR  - P01 CA081534/CA/NCI NIH HHS/United States
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20150720
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Piperidines)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrimidines)
RN  - 1X70OSD4VX (ibrutinib)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - *Abnormal Karyotype
MH  - Adenine/analogs & derivatives
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*therapeutic use
MH  - Chromosome Deletion
MH  - Chromosomes, Human, Pair 17/genetics
MH  - Cytogenetic Analysis
MH  - Female
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy/genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy/genetics
MH  - Piperidines
MH  - Pyrazoles/*therapeutic use
MH  - Pyrimidines/*therapeutic use
MH  - Survival Analysis
MH  - Treatment Outcome
PMC - PMC4866653
MID - NIHMS773424
OTO - NOTNLM
OT  - chronic lymphocytic leukemia (CLL)
OT  - complex karyotype
OT  - del(17p)
OT  - ibrutinib
OT  - relapsed and refractory
COIS- Conflict of interest: SOB and JAB received research funding from Pharmacyclics.
EDAT- 2015/07/22 06:00
MHDA- 2016/01/07 06:00
PMCR- 2016/10/15
CRDT- 2015/07/22 06:00
PHST- 2015/03/06 00:00 [received]
PHST- 2015/05/12 00:00 [accepted]
PHST- 2015/07/22 06:00 [entrez]
PHST- 2015/07/22 06:00 [pubmed]
PHST- 2016/01/07 06:00 [medline]
PHST- 2016/10/15 00:00 [pmc-release]
AID - 10.1002/cncr.29566 [doi]
PST - ppublish
SO  - Cancer. 2015 Oct 15;121(20):3612-21. doi: 10.1002/cncr.29566. Epub 2015 Jul 20.