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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Impact of ibrutinib dose adherence on therapeutic efficacy in patients with previously treated CLL/SLL</title>
<author><name sortKey="Barr, Paul M" sort="Barr, Paul M" uniqKey="Barr P" first="Paul M." last="Barr">Paul M. Barr</name>
<affiliation><nlm:aff id="aff1">Wilmot Cancer Institute, University of Rochester, Rochester, NY;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brown, Jennifer R" sort="Brown, Jennifer R" uniqKey="Brown J" first="Jennifer R." last="Brown">Jennifer R. Brown</name>
<affiliation><nlm:aff id="aff2">Dana-Farber Cancer Institute, Boston, MA;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hillmen, Peter" sort="Hillmen, Peter" uniqKey="Hillmen P" first="Peter" last="Hillmen">Peter Hillmen</name>
<affiliation><nlm:aff id="aff3">The Leeds Teaching Hospitals, St. James Institute of Oncology, Leeds, United Kingdom;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="O Brien, Susan" sort="O Brien, Susan" uniqKey="O Brien S" first="Susan" last="O'Brien">Susan O'Brien</name>
<affiliation><nlm:aff id="aff4">Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Barrientos, Jacqueline C" sort="Barrientos, Jacqueline C" uniqKey="Barrientos J" first="Jacqueline C." last="Barrientos">Jacqueline C. Barrientos</name>
<affiliation><nlm:aff id="aff5">Hofstra Northwell School of Medicine, Hempstead, NY;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Reddy, Nishitha M" sort="Reddy, Nishitha M" uniqKey="Reddy N" first="Nishitha M." last="Reddy">Nishitha M. Reddy</name>
<affiliation><nlm:aff id="aff6">Vanderbilt-Ingram Cancer Center, Nashville, TN;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Coutre, Steven" sort="Coutre, Steven" uniqKey="Coutre S" first="Steven" last="Coutre">Steven Coutre</name>
<affiliation><nlm:aff id="aff7">Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mulligan, Stephen P" sort="Mulligan, Stephen P" uniqKey="Mulligan S" first="Stephen P." last="Mulligan">Stephen P. Mulligan</name>
<affiliation><nlm:aff id="aff8">Royal North Shore Hospital, Sydney, NSW, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jaeger, Ulrich" sort="Jaeger, Ulrich" uniqKey="Jaeger U" first="Ulrich" last="Jaeger">Ulrich Jaeger</name>
<affiliation><nlm:aff id="aff9">Division of Hematology, Department of Medicine I, Medical University of Vienna, Vienna, Austria;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Furman, Richard R" sort="Furman, Richard R" uniqKey="Furman R" first="Richard R." last="Furman">Richard R. Furman</name>
<affiliation><nlm:aff id="aff10">Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cymbalista, Florence" sort="Cymbalista, Florence" uniqKey="Cymbalista F" first="Florence" last="Cymbalista">Florence Cymbalista</name>
<affiliation><nlm:aff id="aff11">Hôpital Avicenne, Paris, France;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Montillo, Marco" sort="Montillo, Marco" uniqKey="Montillo M" first="Marco" last="Montillo">Marco Montillo</name>
<affiliation><nlm:aff id="aff12">Niguarda Ca’ Granda Hospital, Milan, Italy;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Dearden, Claire" sort="Dearden, Claire" uniqKey="Dearden C" first="Claire" last="Dearden">Claire Dearden</name>
<affiliation><nlm:aff id="aff13">Royal Marsden Hospital, London, United Kingdom;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Robak, Tadeusz" sort="Robak, Tadeusz" uniqKey="Robak T" first="Tadeusz" last="Robak">Tadeusz Robak</name>
<affiliation><nlm:aff id="aff14">Department of Hematology, Medical University of Lodz, Lodz, Poland;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Moreno, Carol" sort="Moreno, Carol" uniqKey="Moreno C" first="Carol" last="Moreno">Carol Moreno</name>
<affiliation><nlm:aff id="aff15">Hospital de la Santa Creu Sant Pau, Barcelona, Spain;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pagel, John M" sort="Pagel, John M" uniqKey="Pagel J" first="John M." last="Pagel">John M. Pagel</name>
<affiliation><nlm:aff id="aff16">Swedish Cancer Institute, Seattle, WA;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Burger, Jan A" sort="Burger, Jan A" uniqKey="Burger J" first="Jan A." last="Burger">Jan A. Burger</name>
<affiliation><nlm:aff id="aff4">Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Suzuki, Samuel" sort="Suzuki, Samuel" uniqKey="Suzuki S" first="Samuel" last="Suzuki">Samuel Suzuki</name>
<affiliation><nlm:aff id="aff17">Pharmacyclics LLC, AbbVie, Sunnyvale, CA;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sukbuntherng, Juthamas" sort="Sukbuntherng, Juthamas" uniqKey="Sukbuntherng J" first="Juthamas" last="Sukbuntherng">Juthamas Sukbuntherng</name>
<affiliation><nlm:aff id="aff17">Pharmacyclics LLC, AbbVie, Sunnyvale, CA;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cole, George" sort="Cole, George" uniqKey="Cole G" first="George" last="Cole">George Cole</name>
<affiliation><nlm:aff id="aff17">Pharmacyclics LLC, AbbVie, Sunnyvale, CA;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="James, Danelle F" sort="James, Danelle F" uniqKey="James D" first="Danelle F." last="James">Danelle F. James</name>
<affiliation><nlm:aff id="aff17">Pharmacyclics LLC, AbbVie, Sunnyvale, CA;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Byrd, John C" sort="Byrd, John C" uniqKey="Byrd J" first="John C." last="Byrd">John C. Byrd</name>
<affiliation><nlm:aff id="aff18">The Ohio State University Medical Center, The Ohio State University, Columbus, OH</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">28373262</idno>
<idno type="pmc">5437732</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437732</idno>
<idno type="RBID">PMC:5437732</idno>
<idno type="doi">10.1182/blood-2016-12-737346</idno>
<date when="2017">2017</date>
<idno type="wicri:Area/Pmc/Corpus">001810</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001810</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Impact of ibrutinib dose adherence on therapeutic efficacy in patients with previously treated CLL/SLL</title>
<author><name sortKey="Barr, Paul M" sort="Barr, Paul M" uniqKey="Barr P" first="Paul M." last="Barr">Paul M. Barr</name>
<affiliation><nlm:aff id="aff1">Wilmot Cancer Institute, University of Rochester, Rochester, NY;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brown, Jennifer R" sort="Brown, Jennifer R" uniqKey="Brown J" first="Jennifer R." last="Brown">Jennifer R. Brown</name>
<affiliation><nlm:aff id="aff2">Dana-Farber Cancer Institute, Boston, MA;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hillmen, Peter" sort="Hillmen, Peter" uniqKey="Hillmen P" first="Peter" last="Hillmen">Peter Hillmen</name>
<affiliation><nlm:aff id="aff3">The Leeds Teaching Hospitals, St. James Institute of Oncology, Leeds, United Kingdom;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="O Brien, Susan" sort="O Brien, Susan" uniqKey="O Brien S" first="Susan" last="O'Brien">Susan O'Brien</name>
<affiliation><nlm:aff id="aff4">Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Barrientos, Jacqueline C" sort="Barrientos, Jacqueline C" uniqKey="Barrientos J" first="Jacqueline C." last="Barrientos">Jacqueline C. Barrientos</name>
<affiliation><nlm:aff id="aff5">Hofstra Northwell School of Medicine, Hempstead, NY;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Reddy, Nishitha M" sort="Reddy, Nishitha M" uniqKey="Reddy N" first="Nishitha M." last="Reddy">Nishitha M. Reddy</name>
<affiliation><nlm:aff id="aff6">Vanderbilt-Ingram Cancer Center, Nashville, TN;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Coutre, Steven" sort="Coutre, Steven" uniqKey="Coutre S" first="Steven" last="Coutre">Steven Coutre</name>
<affiliation><nlm:aff id="aff7">Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mulligan, Stephen P" sort="Mulligan, Stephen P" uniqKey="Mulligan S" first="Stephen P." last="Mulligan">Stephen P. Mulligan</name>
<affiliation><nlm:aff id="aff8">Royal North Shore Hospital, Sydney, NSW, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jaeger, Ulrich" sort="Jaeger, Ulrich" uniqKey="Jaeger U" first="Ulrich" last="Jaeger">Ulrich Jaeger</name>
<affiliation><nlm:aff id="aff9">Division of Hematology, Department of Medicine I, Medical University of Vienna, Vienna, Austria;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Furman, Richard R" sort="Furman, Richard R" uniqKey="Furman R" first="Richard R." last="Furman">Richard R. Furman</name>
<affiliation><nlm:aff id="aff10">Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cymbalista, Florence" sort="Cymbalista, Florence" uniqKey="Cymbalista F" first="Florence" last="Cymbalista">Florence Cymbalista</name>
<affiliation><nlm:aff id="aff11">Hôpital Avicenne, Paris, France;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Montillo, Marco" sort="Montillo, Marco" uniqKey="Montillo M" first="Marco" last="Montillo">Marco Montillo</name>
<affiliation><nlm:aff id="aff12">Niguarda Ca’ Granda Hospital, Milan, Italy;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Dearden, Claire" sort="Dearden, Claire" uniqKey="Dearden C" first="Claire" last="Dearden">Claire Dearden</name>
<affiliation><nlm:aff id="aff13">Royal Marsden Hospital, London, United Kingdom;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Robak, Tadeusz" sort="Robak, Tadeusz" uniqKey="Robak T" first="Tadeusz" last="Robak">Tadeusz Robak</name>
<affiliation><nlm:aff id="aff14">Department of Hematology, Medical University of Lodz, Lodz, Poland;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Moreno, Carol" sort="Moreno, Carol" uniqKey="Moreno C" first="Carol" last="Moreno">Carol Moreno</name>
<affiliation><nlm:aff id="aff15">Hospital de la Santa Creu Sant Pau, Barcelona, Spain;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pagel, John M" sort="Pagel, John M" uniqKey="Pagel J" first="John M." last="Pagel">John M. Pagel</name>
<affiliation><nlm:aff id="aff16">Swedish Cancer Institute, Seattle, WA;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Burger, Jan A" sort="Burger, Jan A" uniqKey="Burger J" first="Jan A." last="Burger">Jan A. Burger</name>
<affiliation><nlm:aff id="aff4">Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Suzuki, Samuel" sort="Suzuki, Samuel" uniqKey="Suzuki S" first="Samuel" last="Suzuki">Samuel Suzuki</name>
<affiliation><nlm:aff id="aff17">Pharmacyclics LLC, AbbVie, Sunnyvale, CA;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sukbuntherng, Juthamas" sort="Sukbuntherng, Juthamas" uniqKey="Sukbuntherng J" first="Juthamas" last="Sukbuntherng">Juthamas Sukbuntherng</name>
<affiliation><nlm:aff id="aff17">Pharmacyclics LLC, AbbVie, Sunnyvale, CA;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cole, George" sort="Cole, George" uniqKey="Cole G" first="George" last="Cole">George Cole</name>
<affiliation><nlm:aff id="aff17">Pharmacyclics LLC, AbbVie, Sunnyvale, CA;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="James, Danelle F" sort="James, Danelle F" uniqKey="James D" first="Danelle F." last="James">Danelle F. James</name>
<affiliation><nlm:aff id="aff17">Pharmacyclics LLC, AbbVie, Sunnyvale, CA;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Byrd, John C" sort="Byrd, John C" uniqKey="Byrd J" first="John C." last="Byrd">John C. Byrd</name>
<affiliation><nlm:aff id="aff18">The Ohio State University Medical Center, The Ohio State University, Columbus, OH</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Blood</title>
<idno type="ISSN">0006-4971</idno>
<idno type="eISSN">1528-0020</idno>
<imprint><date when="2017">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>Key Points</title>
<p><list list-type="bullet"><list-item><p>Higher ibrutinib DI is associated with improved PFS, independent of del17p or <italic>TP53</italic>
mutation.</p>
</list-item>
<list-item><p>Ibrutinib hold for >1 week, often needed to manage adverse events, is associated with increased PFS events.</p>
</list-item>
</list>
</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Blood</journal-id>
<journal-id journal-id-type="iso-abbrev">Blood</journal-id>
<journal-id journal-id-type="hwp">bloodjournal</journal-id>
<journal-id journal-id-type="pmc">blood</journal-id>
<journal-id journal-id-type="publisher-id">Blood</journal-id>
<journal-title-group><journal-title>Blood</journal-title>
</journal-title-group>
<issn pub-type="ppub">0006-4971</issn>
<issn pub-type="epub">1528-0020</issn>
<publisher><publisher-name>American Society of Hematology</publisher-name>
<publisher-loc>Washington, DC</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">28373262</article-id>
<article-id pub-id-type="pmc">5437732</article-id>
<article-id pub-id-type="publisher-id">2016/737346</article-id>
<article-id pub-id-type="doi">10.1182/blood-2016-12-737346</article-id>
<article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>29</subject>
<subject>8</subject>
<subject>39</subject>
</subj-group>
<subj-group subj-group-type="heading"><subject>Clinical Trials and Observations</subject>
</subj-group>
</article-categories>
<title-group><article-title>Impact of ibrutinib dose adherence on therapeutic efficacy in patients with previously treated CLL/SLL</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0002-9733-401X</contrib-id>
<name><surname>Barr</surname>
<given-names>Paul M.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brown</surname>
<given-names>Jennifer R.</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hillmen</surname>
<given-names>Peter</given-names>
</name>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>O'Brien</surname>
<given-names>Susan</given-names>
</name>
<xref ref-type="aff" rid="aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Barrientos</surname>
<given-names>Jacqueline C.</given-names>
</name>
<xref ref-type="aff" rid="aff5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Reddy</surname>
<given-names>Nishitha M.</given-names>
</name>
<xref ref-type="aff" rid="aff6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Coutre</surname>
<given-names>Steven</given-names>
</name>
<xref ref-type="aff" rid="aff7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mulligan</surname>
<given-names>Stephen P.</given-names>
</name>
<xref ref-type="aff" rid="aff8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jaeger</surname>
<given-names>Ulrich</given-names>
</name>
<xref ref-type="aff" rid="aff9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Furman</surname>
<given-names>Richard R.</given-names>
</name>
<xref ref-type="aff" rid="aff10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cymbalista</surname>
<given-names>Florence</given-names>
</name>
<xref ref-type="aff" rid="aff11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Montillo</surname>
<given-names>Marco</given-names>
</name>
<xref ref-type="aff" rid="aff12">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dearden</surname>
<given-names>Claire</given-names>
</name>
<xref ref-type="aff" rid="aff13">13</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Robak</surname>
<given-names>Tadeusz</given-names>
</name>
<xref ref-type="aff" rid="aff14">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Moreno</surname>
<given-names>Carol</given-names>
</name>
<xref ref-type="aff" rid="aff15">15</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pagel</surname>
<given-names>John M.</given-names>
</name>
<xref ref-type="aff" rid="aff16">16</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Burger</surname>
<given-names>Jan A.</given-names>
</name>
<xref ref-type="aff" rid="aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Suzuki</surname>
<given-names>Samuel</given-names>
</name>
<xref ref-type="aff" rid="aff17">17</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sukbuntherng</surname>
<given-names>Juthamas</given-names>
</name>
<xref ref-type="aff" rid="aff17">17</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cole</surname>
<given-names>George</given-names>
</name>
<xref ref-type="aff" rid="aff17">17</xref>
</contrib>
<contrib contrib-type="author"><name><surname>James</surname>
<given-names>Danelle F.</given-names>
</name>
<xref ref-type="aff" rid="aff17">17</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Byrd</surname>
<given-names>John C.</given-names>
</name>
<xref ref-type="aff" rid="aff18">18</xref>
</contrib>
<aff id="aff1"><label>1</label>
Wilmot Cancer Institute, University of Rochester, Rochester, NY;</aff>
<aff id="aff2"><label>2</label>
Dana-Farber Cancer Institute, Boston, MA;</aff>
<aff id="aff3"><label>3</label>
The Leeds Teaching Hospitals, St. James Institute of Oncology, Leeds, United Kingdom;</aff>
<aff id="aff4"><label>4</label>
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX;</aff>
<aff id="aff5"><label>5</label>
Hofstra Northwell School of Medicine, Hempstead, NY;</aff>
<aff id="aff6"><label>6</label>
Vanderbilt-Ingram Cancer Center, Nashville, TN;</aff>
<aff id="aff7"><label>7</label>
Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA;</aff>
<aff id="aff8"><label>8</label>
Royal North Shore Hospital, Sydney, NSW, Australia;</aff>
<aff id="aff9"><label>9</label>
Division of Hematology, Department of Medicine I, Medical University of Vienna, Vienna, Austria;</aff>
<aff id="aff10"><label>10</label>
Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY;</aff>
<aff id="aff11"><label>11</label>
Hôpital Avicenne, Paris, France;</aff>
<aff id="aff12"><label>12</label>
Niguarda Ca’ Granda Hospital, Milan, Italy;</aff>
<aff id="aff13"><label>13</label>
Royal Marsden Hospital, London, United Kingdom;</aff>
<aff id="aff14"><label>14</label>
Department of Hematology, Medical University of Lodz, Lodz, Poland;</aff>
<aff id="aff15"><label>15</label>
Hospital de la Santa Creu Sant Pau, Barcelona, Spain;</aff>
<aff id="aff16"><label>16</label>
Swedish Cancer Institute, Seattle, WA;</aff>
<aff id="aff17"><label>17</label>
Pharmacyclics LLC, AbbVie, Sunnyvale, CA;</aff>
<aff id="aff18"><label>18</label>
The Ohio State University Medical Center, The Ohio State University, Columbus, OH</aff>
</contrib-group>
<pub-date pub-type="ppub"><day>11</day>
<month>5</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="epreprint"><day>03</day>
<month>4</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>11</day>
<month>5</month>
<year>2017</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the . </pmc-comment>
<volume>129</volume>
<issue>19</issue>
<fpage>2612</fpage>
<lpage>2615</lpage>
<history><date date-type="received"><day>19</day>
<month>12</month>
<year>2016</year>
</date>
<date date-type="accepted"><day>20</day>
<month>3</month>
<year>2017</year>
</date>
</history>
<permissions><copyright-statement>© 2017 by The American Society of Hematology</copyright-statement>
<copyright-year>2017</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:href="blood737346.pdf"></self-uri>
<abstract abstract-type="executive-summary"><title>Key Points</title>
<p><list list-type="bullet"><list-item><p>Higher ibrutinib DI is associated with improved PFS, independent of del17p or <italic>TP53</italic>
mutation.</p>
</list-item>
<list-item><p>Ibrutinib hold for >1 week, often needed to manage adverse events, is associated with increased PFS events.</p>
</list-item>
</list>
</p>
</abstract>
<abstract><p>Ibrutinib, an oral inhibitor of Bruton’s tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that was maintained at 24 hours. It is unknown if intermittent interruption of ibrutinib therapy contributes to altered clinical outcomes. We therefore evaluated the effect of ibrutinib dose adherence on patient outcomes in the phase 3 RESONATE trial. The overall mean dose intensity (DI) was 95% with median treatment duration of ∼9 months. Pharmacokinetic assessment of ibrutinib exposure at 420-mg dose suggested similar exposure regardless of patient weight or age. As assessed by independent review committee, patients with higher DI experienced longer median progression-free survival (PFS) compared with those with lower DI regardless of del17p and/or <italic>TP53</italic>
status. Of 79 patients requiring a drug hold, treatment was restarted at the original dose in 73 (92%) patients. Mean duration of a missed-dose event was 18.7 days (range, 8-56). Patients missing ≥8 consecutive days of ibrutinib had a shorter median PFS vs those missing <8 days (10.9 months vs not reached). These results support sustained adherence to once-daily ibrutinib dosing at 420 mg as clinically feasible to achieve optimal outcomes in patients with previously treated CLL. The trial was registered at <ext-link ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</ext-link>
as #NCT01578707.</p>
</abstract>
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</front>
</pmc>
</record>
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