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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\u003EPatients with myelodysplastic syndrome and chronic myelomonocytic leukemia, particularly those with high risk disease, have an unmet therapeutic need. Azacitidine monotherapy results in a modest response rate and duration of response. The addition of vorinostat or lenalidomide to azacytidine does not improve overall response rates, but may improve disease-free survival, does increase toxicity, discontinuations, and dose-reductions.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Emyelodysplastic syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Echronic myelomonocytic leukemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eprognosis\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecombination treatment\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group drug\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eazacitidine\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Elenalidomide\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Evorinostat\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EAzacitidine With or Without Lenalidomide or Vorinostat in Treating Patients With Higher-Risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EPatients with higher-risk myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) have a dismal prognosis; median survival in this patient population has been reported as \u22641.2 years, as cited in a 1997 study by Greenberg and colleagues. There is only one randomized study of azacitidine (AZA) in MDS showing a median survival of 24.5 months for AZA vs 15.1 months for conventional care regimens (HR, 0.58; CI, 0.43 to 0.77; log-rank \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.0001) [Fenaux P et al. \u003Cem\u003ELancet Oncology\u003C\/em\u003E. 2009].\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EHistone deacetylase inhibitors such as vorinostat (VOR) act synergistically with hypomethylating agents like AZA. A phase 1\/2 study of VOR added to AZA in MDS in 33 evaluable patients showed a response of 70%, a complete response (CR) rate of 42%, and a median duration of response (DOR) of 16 months [Silverman LR et al. ASH 2013 (abstr 386)]. Lenalidomide (LEN) added to AZA in a phase 2 study in MDS (n\u2009=\u200936) resulted in an overall response rate (ORR) of 72%, a CR rate of 44%, and a DOR of \u0026gt;\u200917 months [Sekeres MA et al. \u003Cem\u003EBlood\u003C\/em\u003E. 2012]. AZA and LEN have nonoverlapping mechanisms of action.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EMikkael Sekeres, MD, Cleveland Clinic, Cleveland, Ohio, USA, reported on the Azacitidine With or Without Lenalidomide or Vorinostat in Treating Patients With Higher-Risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia study [Sekeres MA et al. ASH 2014 (abstr LBA-5)]. Groups participating in the study included the Southwest Oncology Group, Alliance, the Eastern Cooperative Oncology Group, and the National Cancer Institute of Canada.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EPatients with higher-risk MDS or CMML were randomly assigned to AZA 75 mg\/m\u003Csup\u003E2\u003C\/sup\u003E\/day days 1 to 7 (n\u2009=\u200992), AZA plus LEN 10 mg\/day for 21 days (n\u2009=\u200993), or AZA plus VOR 300 mg BID days 3 to 9 (n\u2009=\u200991). The primary objective was 20% improvement of ORR. Secondary objectives were improvements in overall survival (OS), relapse-free survival, and leukemia-free survival.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EThe 3 study arms were similar in patient characteristics. The mean age was 70 years; about 18% of patients had CMML, and about 7% had therapy-related MDS. Grade 3 or higher toxicities for the safety population (n\u2009=\u2009260) are summarized in \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E.\u003C\/p\u003E\n         \u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/11634\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/11634\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11634\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EGrade \u2265\u20093 Toxicities Results\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EResponses are summarized in \u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E.\u003C\/p\u003E\n         \u003Cdiv id=\u0022T2\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/11636\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/11636\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11636\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003EResponses to Treatment Results\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EThere were no differences in ORR or other response criteria comparing AZA plus LEN or AZA plus VOR to AZA monotherapy. Dr Sekeres said that some subgroups may have benefitted from AZA-based combinations, as the hematologic improvement rates for neutrophils were higher for patients receiving the AZA plus LEN combination (\u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.05), as were response rates for CMML patients compared to AZA monotherapy, although the limited number in this subgroup precluded adequate power to show a significant difference (59% vs 33%, \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.15). Analyses by cytogenetic subgroups are pending. A strong signal for improved disease-free survival (DFS) was seen for the AZA plus VOR combination compared to AZA monotherapy (median 13 months vs 7 months, \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.11).\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EAn open question is whether combination therapies in MDS are too toxic or whether toxicities need to be managed better. In this study, the investigators thought the toxicities were more severe than was reported by patients. It is possible that DOR and OS may be better end points for large MDS trials. In this trial, time to response was not assessed.\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\/13.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?nzo9y1\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzo9y1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}