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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThe outcome of patients with chronic lymphocytic leukemia treated with ibrutinib-based regimens indicates that complex metaphase karyotype is a more important predictor of outcome than del(17p). Lack of complex karyotype is associated with less-frequent disease progression. Patients with complex karyotype may be an ideal group in which to study novel treatments.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ecomplex metaphase karyotype\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Einferiority\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Echronic lymphocytic leukemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Erelapse\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Efludarabine-refractory\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group drug\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eibrutinib\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Efludarabine\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EPhilip A. Thompson, MBBS, University of Texas MD Anderson Cancer Center, Houston, Texas, USA, reported that complex metaphase karyotype (CKT), defined as \u2265\u20093 unrelated abnormalities, rather than del(17p), is linked with inferior outcomes in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib who relapse or are fludarabine-refractory.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EIbrutinib has robustly increased progression-free survival (PFS) in CLL [Byrd JC et al. \u003Cem\u003EN Engl J Med.\u003C\/em\u003E 2013], although patients with deletions in the short arm of chromosome 17 remain a high-risk group. In CLL, del(17p) is often associated with CKT involving multiple unrelated abnormalities [Haferlach T et al. \u003Cem\u003ELeukemia.\u003C\/em\u003E 2007]. Genes conferring treatment resistance exist in patients with del(17p) and\/or CKT [Woyach JA et al. \u003Cem\u003EN Engl J Med.\u003C\/em\u003E 2014]. The significance of CKT in the outcome of ibrutinib treatment of CLL is unclear.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EThis study analyzed 100 CLL patients (median age 65 years) treated a median of twice with ibrutinib-based regimens from mid-2010 to mid-2013. The majority of patients (60%) were Rai stage III-IV and lacked immunoglobulin heavy chain variable mutations (81%). A minority (19%) were refractory to fludarabine therapy. Use of fluorescence in-situ hybridization (FISH) revealed prevalence of del(17p), del(11q), CKT, and other mutations in 48%, 28%, 42%, and 24% of patients, respectively. Of the 32 patients with del(17p) and 33 with no del(17p) for whom metaphase karyotype data were available, 23 and 4, respectively, harbored CKT.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThe median follow-up was 27 months (range, 11 to 48 months). Eight patients who underwent planned allogeneic stem cell transplant were censored for event-free survival (EFS) analysis. In 36 patients treated with ibrutinib\u2009+\u2009rituximab, complete response rate (CRR) was 8%. In 14 patients treated with ibrutinib\u2009+\u2009bendamustine\u2009+\u2009rituximab, CRR was 50% (\u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.001), and the significance remained in multivariable analysis. Overall rates and CRRs did not differ significantly between patients with or without del(17p), del(11q), and other mutations, or those with or without CKT. The presence of del(17p) was associated with significantly worse EFS.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EEFS was also significantly worse for patients with CKT vs no complex karyotype (12\/27 vs 31\/38; \u003Cem\u003EP\u003C\/em\u003E\u2009\u0026lt;\u2009.0001) and in patients with del(17p) and CKT vs those with del(17p) alone (11\/23 vs 7\/9; \u003Cem\u003EP\u2009\u003C\/em\u003E=\u2009.047). In the absence of CKT, patients with del(17p) or del(11q) had similar EFS (7\/9 vs 9\/10; \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.516). Multivariable analysis revealed the significant association of CKT with EFS (HR, 5.3; 95% CI, 1.5 to 19.2; \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.011).\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EThe most frequent event was progression of CLL (n\u2009=\u200910), followed by death (n\u2009=\u20098), and Richter transformation (n\u2009=\u20095). In 27 patients with CKT and 38 patients without CKT, CLL progression was evident in 5 and 1 patients, respectively. Overall survival in all patients was not significantly different.\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EPatients refractory to fludarabine had significantly worse overall survival (10 of 19 died) than those not refractory to fludarabine (19 of 81 died) (\u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.009). Multivariable analysis revealed significant association of fludarabine-refractory disease with worse overall survival (HR, 6.4; 95% CI, 1.8 to 22.8; \u003Cem\u003EP\u2009\u003C\/em\u003E=\u2009.004).\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EThe data implicate CKT as a more important predictor of outcome than del(17p). Absence of CKT is associated with less frequent disease progression. When progression occurs, it tends to occur \u0026gt;\u200912 months after ibrutinib treatment, with death soon after.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EThe researchers concluded that patients with CKT are an ideal group in which to study novel treatments.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/55\/16.2.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzo9zp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}