115 lines
36 KiB
Text
115 lines
36 KiB
Text
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" class="no-js no-jr">
|
|
<head>
|
|
<!-- For pinger, set start time and add meta elements. -->
|
|
<script type="text/javascript">var ncbi_startTime = new Date();</script>
|
|
|
|
<!-- Logger begin -->
|
|
<meta name="ncbi_db" content="books">
|
|
<meta name="ncbi_pdid" content="book-part">
|
|
<meta name="ncbi_acc" content="NBK548759">
|
|
<meta name="ncbi_domain" content="livertox">
|
|
<meta name="ncbi_report" content="reader">
|
|
<meta name="ncbi_type" content="fulltext">
|
|
<meta name="ncbi_objectid" content="">
|
|
<meta name="ncbi_pcid" content="/NBK548759/?report=reader">
|
|
<meta name="ncbi_pagename" content="Daratumumab - LiverTox - NCBI Bookshelf">
|
|
<meta name="ncbi_bookparttype" content="chapter">
|
|
<meta name="ncbi_app" content="bookshelf">
|
|
<!-- Logger end -->
|
|
|
|
<!--component id="Page" label="meta"/-->
|
|
<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Daratumumab - LiverTox - NCBI Bookshelf</title>
|
|
<meta charset="utf-8">
|
|
<meta name="apple-mobile-web-app-capable" content="no">
|
|
<meta name="viewport" content="initial-scale=1,minimum-scale=1,maximum-scale=1,user-scalable=no">
|
|
<meta name="jr-col-layout" content="auto">
|
|
<meta name="jr-prev-unit" content="/books/n/livertox/Daptomycin/?report=reader">
|
|
<meta name="jr-next-unit" content="/books/n/livertox/Daridorexant/?report=reader">
|
|
<meta name="bk-toc-url" content="/books/n/livertox/?report=toc">
|
|
<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE">
|
|
<meta name="citation_inbook_title" content="LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]">
|
|
<meta name="citation_title" content="Daratumumab">
|
|
<meta name="citation_publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases">
|
|
<meta name="citation_date" content="2017/05/25">
|
|
<meta name="citation_pmid" content="31644068">
|
|
<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK548759/">
|
|
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/">
|
|
<meta name="DC.Title" content="Daratumumab">
|
|
<meta name="DC.Type" content="Text">
|
|
<meta name="DC.Publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases">
|
|
<meta name="DC.Date" content="2017/05/25">
|
|
<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK548759/">
|
|
<meta name="description" content="Daratumumab is a human monoclonal antibody to CD38 which is used in combination with other antineoplastic agents in the therapy of multiple myeloma. Daratumumab has been implicated in instances of transient, mild-to-moderate serum enzyme elevations, but has not been linked to cases of clinically apparent liver injury with jaundice.">
|
|
<meta name="og:title" content="Daratumumab">
|
|
<meta name="og:type" content="book">
|
|
<meta name="og:description" content="Daratumumab is a human monoclonal antibody to CD38 which is used in combination with other antineoplastic agents in the therapy of multiple myeloma. Daratumumab has been implicated in instances of transient, mild-to-moderate serum enzyme elevations, but has not been linked to cases of clinically apparent liver injury with jaundice.">
|
|
<meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK548759/">
|
|
<meta name="og:site_name" content="NCBI Bookshelf">
|
|
<meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-livertox-lrg.png">
|
|
<meta name="twitter:card" content="summary">
|
|
<meta name="twitter:site" content="@ncbibooks">
|
|
<meta name="bk-non-canon-loc" content="/books/n/livertox/Daratumumab/?report=reader">
|
|
<link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK548759/">
|
|
<link href="https://fonts.googleapis.com/css?family=Archivo+Narrow:400,700,400italic,700italic&subset=latin" rel="stylesheet" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/libs.min.css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/jr.min.css">
|
|
<meta name="format-detection" content="telephone=no">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css//books_print.min.css" type="text/css" media="print">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_reader.min.css" type="text/css">
|
|
<style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style>
|
|
|
|
<link rel="shortcut icon" href="//www.ncbi.nlm.nih.gov/favicon.ico">
|
|
<meta name="ncbi_phid" content="CE8B33157D7F92B10000000000E700B3.m_5">
|
|
<meta name='referrer' content='origin-when-cross-origin'/><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3852956/3849091.css"></head>
|
|
<body>
|
|
<!-- Book content! -->
|
|
|
|
|
|
<div id="jr" data-jr-path="/corehtml/pmc/jatsreader/ptpmc_3.22/"><div class="jr-unsupported"><table class="modal"><tr><td><span class="attn inline-block"></span><br />Your browser does not support the NLM PubReader view.<br />Go to <a href="/pmc/about/pr-browsers/">this page</a> to see a list of supported browsers<br />or return to the <br /><a href="/books/NBK548759/?report=classic">regular view</a>.</td></tr></table></div><div id="jr-ui" class="hidden"><nav id="jr-head"><div class="flexh tb"><div id="jr-tb1"><a id="jr-links-sw" class="hidden" title="Links"><svg xmlns="http://www.w3.org/2000/svg" version="1.1" x="0px" y="0px" viewBox="0 0 70.6 85.3" style="enable-background:new 0 0 70.6 85.3;vertical-align:middle" xml:space="preserve" width="24" height="24">
|
|
<style type="text/css">.st0{fill:#939598;}</style>
|
|
<g>
|
|
<path class="st0" d="M36,0C12.8,2.2-22.4,14.6,19.6,32.5C40.7,41.4-30.6,14,35.9,9.8"></path>
|
|
<path class="st0" d="M34.5,85.3c23.2-2.2,58.4-14.6,16.4-32.5c-21.1-8.9,50.2,18.5-16.3,22.7"></path>
|
|
<path class="st0" d="M34.7,37.1c66.5-4.2-4.8-31.6,16.3-22.7c42.1,17.9,6.9,30.3-16.4,32.5h1.7c-66.2,4.4,4.8,31.6-16.3,22.7 c-42.1-17.9-6.9-30.3,16.4-32.5"></path>
|
|
</g>
|
|
</svg> Books</a></div><div class="jr-rhead f1 flexh"><div class="head"><a href="/books/n/livertox/Daptomycin/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="body"><div class="t">Daratumumab</div><div class="j">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]</div></div><div class="tail"><a href="/books/n/livertox/Daridorexant/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 h-55.484l-10.662,29.981c-4.065,11.431-12.794,20.627-24.001,25.274c-0.005,0.002-0.009,0.004-0.014,0.005 c-11.235,4.66-23.919,4.333-34.905-0.889l-28.723-13.653l-39.234,39.234l13.653,28.721c5.219,10.979,5.545,23.681,0.889,34.91 c-0.002,0.004-0.004,0.009-0.006,0.013c-4.649,11.214-13.834,19.931-25.271,23.998L50,228.257v55.485l29.98,10.661 c11.431,4.065,20.627,12.794,25.274,24c0.002,0.005,0.003,0.01,0.005,0.014c4.66,11.236,4.334,23.921-0.888,34.906l-13.654,28.723 l39.234,39.234l28.721-13.652c10.979-5.219,23.681-5.546,34.909-0.889c0.005,0.002,0.01,0.004,0.014,0.006 c11.214,4.649,19.93,13.833,23.998,25.271L228.257,462h55.484l10.595-29.79c4.103-11.538,12.908-20.824,24.216-25.525 c0.005-0.002,0.009-0.004,0.014-0.006c11.127-4.628,23.694-4.311,34.578,0.863l28.902,13.738l39.234-39.234l-13.66-28.737 c-5.214-10.969-5.539-23.659-0.886-34.877c0.002-0.005,0.004-0.009,0.006-0.014c4.654-11.225,13.848-19.949,25.297-24.021 L462,283.742z M256,331.546c-41.724,0-75.548-33.823-75.548-75.546s33.824-75.547,75.548-75.547 c41.723,0,75.546,33.824,75.546,75.547S297.723,331.546,256,331.546z"></path></svg></a><a id="jr-fip-sw" class="btn wsprkl hidden" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-rtoc-sw" class="btn wsprkl hidden" title="Table of Contents"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,20h10v8H20V20zM36,20h44v8H36V20zM20,37.33h10v8H20V37.33zM36,37.33h44v8H36V37.33zM20,54.66h10v8H20V54.66zM36,54.66h44v8H36V54.66zM20,72h10v8 H20V72zM36,72h44v8H36V72z"></path></svg></a></div></div></nav><nav id="jr-dash" class="noselect"><nav id="jr-dash" class="noselect"><div id="jr-pi" class="hidden"><a id="jr-pi-prev" class="hidden" title="Previous page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a><div class="pginfo">Page <i class="jr-pg-pn">0</i> of <i class="jr-pg-lp">0</i></div><a id="jr-pi-next" class="hidden" title="Next page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div><div id="jr-is-tb"><a id="jr-is-sw" class="btn wsprkl hidden" title="Switch between Figures/Tables strip and Progress bar"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><rect x="10" y="40" width="20" height="20"></rect><rect x="40" y="40" width="20" height="20"></rect><rect x="70" y="40" width="20" height="20"></rect></svg></a></div><nav id="jr-istrip" class="istrip hidden"><a id="jr-is-prev" href="#" class="hidden" title="Previous"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M80,40 60,65 80,90 70,90 50,65 70,40z M50,40 30,65 50,90 40,90 20,65 40,40z"></path><text x="35" y="25" textLength="60" style="font-size:25px">Prev</text></svg></a><a id="jr-is-next" href="#" class="hidden" title="Next"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,40 40,65 20,90 30,90 50,65 30,40z M50,40 70,65 50,90 60,90 80,65 60,40z"></path><text x="15" y="25" textLength="60" style="font-size:25px">Next</text></svg></a></nav><nav id="jr-progress"></nav></nav></nav><aside id="jr-links-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">NCBI Bookshelf</div></div><div class="cnt lol f1"><a href="/books/">Home</a><a href="/books/browse/">Browse All Titles</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://www.facebook.com/sharer/sharer.php?u=https://www.ncbi.nlm.nih.gov/books/NBK548759/"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24" preserveAspectRatio="none"><g><path d="M 17.996,32L 12,32 L 12,16 l-4,0 l0-5.514 l 4-0.002l-0.006-3.248C 11.993,2.737, 13.213,0, 18.512,0l 4.412,0 l0,5.515 l-2.757,0 c-2.063,0-2.163,0.77-2.163,2.209l-0.008,2.76l 4.959,0 l-0.585,5.514L 18,16L 17.996,32z"></path></g></svg> Share on Facebook</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://twitter.com/intent/tweet?url=https://www.ncbi.nlm.nih.gov/books/NBK548759/&text=Daratumumab"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24"><g><path d="M 32,6.076c-1.177,0.522-2.443,0.875-3.771,1.034c 1.355-0.813, 2.396-2.099, 2.887-3.632 c-1.269,0.752-2.674,1.299-4.169,1.593c-1.198-1.276-2.904-2.073-4.792-2.073c-3.626,0-6.565,2.939-6.565,6.565 c0,0.515, 0.058,1.016, 0.17,1.496c-5.456-0.274-10.294-2.888-13.532-6.86c-0.565,0.97-0.889,2.097-0.889,3.301 c0,2.278, 1.159,4.287, 2.921,5.465c-1.076-0.034-2.088-0.329-2.974-0.821c-0.001,0.027-0.001,0.055-0.001,0.083 c0,3.181, 2.263,5.834, 5.266,6.438c-0.551,0.15-1.131,0.23-1.73,0.23c-0.423,0-0.834-0.041-1.235-0.118 c 0.836,2.608, 3.26,4.506, 6.133,4.559c-2.247,1.761-5.078,2.81-8.154,2.81c-0.53,0-1.052-0.031-1.566-0.092 c 2.905,1.863, 6.356,2.95, 10.064,2.95c 12.076,0, 18.679-10.004, 18.679-18.68c0-0.285-0.006-0.568-0.019-0.849 C 30.007,8.548, 31.12,7.392, 32,6.076z"></path></g></svg> Share on Twitter</a></div></aside><aside id="jr-rtoc-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Table of Content</div></div><div class="cnt lol f1"><a href="/books/n/livertox/?report=reader">Title Information</a><a href="/books/n/livertox/toc/?report=reader">Table of Contents Page</a></div></aside><aside id="jr-help-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Settings</div></div><div class="cnt f1"><div id="jr-typo-p" class="typo"><div><a class="sf btn wsprkl">A-</a><a class="lf btn wsprkl">A+</a></div><div><a class="bcol-auto btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 200 100" preserveAspectRatio="none"><text x="10" y="70" style="font-size:60px;font-family: Trebuchet MS, ArialMT, Arial, sans-serif" textLength="180">AUTO</text></svg></a><a class="bcol-1 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M15,25 85,25zM15,40 85,40zM15,55 85,55zM15,70 85,70z"></path></svg></a><a class="bcol-2 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M5,25 45,25z M55,25 95,25zM5,40 45,40z M55,40 95,40zM5,55 45,55z M55,55 95,55zM5,70 45,70z M55,70 95,70z"></path></svg></a></div></div><div class="lol"><a class="" href="/books/NBK548759/?report=classic">Switch to classic view</a><a href="/books/NBK548759/pdf/Bookshelf_NBK548759.pdf">PDF (89K)</a><a href="/books/NBK548759/?report=printable">Print View</a></div></div></aside><aside id="jr-bkhelp-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Help</div></div><div class="cnt f1 lol"><a id="jr-helpobj-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/help.xml" href="">Help</a><a href="mailto:info@ncbi.nlm.nih.gov?subject=PubReader%20feedback%20%2F%20NBK548759%20%2F%20sid%3ACE8B5AF87C7FFCB1_0191SID%20%2F%20phid%3ACE8B33157D7F92B10000000000E700B3.4">Send us feedback</a><a id="jr-about-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/about.xml" href="">About PubReader</a></div></aside><aside id="jr-objectbox" class="thidden hidden"><div class="jr-objectbox-close wsprkl">✘</div><div class="jr-objectbox-inner cnt"><div class="jr-objectbox-drawer"></div></div></aside><nav id="jr-pm-left" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Previous Page</text></svg></nav><nav id="jr-pm-right" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Next Page</text></svg></nav><nav id="jr-fip" class="hidden"><nav id="jr-fip-term-p"><input type="search" placeholder="search this page" id="jr-fip-term" autocorrect="off" autocomplete="off" /><a id="jr-fip-mg" class="wsprkl btn" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-fip-done" class="wsprkl btn" title="Dismiss find">✘</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK548759_"><span class="title" itemprop="name">Daratumumab</span></h1><p class="fm-aai"><a href="#_NBK548759_pubdet_">Publication Details</a></p></div></div><div class="body-content whole_rhythm" itemprop="text"><div id="Daratumumab.OVERVIEW"><h2 id="_Daratumumab_OVERVIEW_">OVERVIEW</h2><div id="Daratumumab.Introduction"><h3>Introduction</h3><p>Daratumumab is a human monoclonal antibody to CD38 which is used in combination with other antineoplastic agents in the therapy of multiple myeloma. Daratumumab has been implicated in instances of transient, mild-to-moderate serum enzyme elevations, but has not been linked to cases of clinically apparent liver injury with jaundice.</p></div><div id="Daratumumab.Background"><h3>Background</h3><p>Daratumumab (dar" a toom' ue mab) is human IgG1 monoclonal antibody to CD38, which is a transmembrane glycoprotein that is frequently overexpressed on cancer cells including multiple myeloma cells. The monoclonal antibody binds to the CD38 molecule and triggers cell apoptosis, probably as a result of antibody mediated cytotoxicity. Daratumumab has been evaluated in heavily pretreated patients with refractory multiple myeloma and shown overall response rates of higher than expected. Daratumumab was given accelerated approval in the United States in 2015 for use in multiple myeloma. Current indications are as therapy of patients with refractory multiple myeloma in combination with lenalidomide (or bortezomib) and dexamethasone or as monotherapy in patients who have failed at least three previous regimens. Daratumumab is available as a solution for intravenous infusion in single use vials of 100 mg in 5 mL or 400 mg in 20 mL (20 mg/mL). The recommended dose is 16 mg/kg intravenously every week for 8 to 9 weeks, and then every 2, 3 or 4 weeks based upon indications and other agents being used. Premedication with methylprednisolone is recommended. Side effects are common and can include infusion reactions, bone marrow suppression, fatigue, nausea and vomiting, diarrhea, muscle spasms, back pain, fever, cough, dyspnea, peripheral edema, peripheral neuropathy and upper respiratory infection. Rare, but potentially serious side effects include severe infusion reactions, neutropenia, thrombocytopenia and interference with cross matching and red blood cell antibody screening.</p></div><div id="Daratumumab.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>In summary analyses of the registration trials of daratumumab for multiple myeloma, 15% of patients developed elevations in ALT during therapy, 13% alkaline phosphatase and 7% bilirubin. The abnormalities were generally mild-to-moderate, transient and asymptomatic. ALT elevations above 5 times the upper limit of normal occurred in less than 1% of patients. In these studies, daratumumab was given with lenalidomide and dexamethasone, and similar rates of liver enzyme elevations occurred with those agents alone without the monoclonal antibody. There were no instances of clinically apparent liver injury with jaundice attributable to daratumumab in these trials and no patient stopped therapy because of hepatic adverse events. Since its approval and more general use, there have been no published reports of clinically apparent liver injury due to daratumumab, and its product label does not list hepatotoxicity as an adverse event.</p><p>Likelihood score: E (unlikely cause of clinically apparent liver injury).</p></div><div id="Daratumumab.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>The mechanism by which daratumumab might cause liver injury is not known. There is no evidence that CD38 is expressed on hepatocytes. Like other monoclonal antibodies, daratumumab is unlikely to have intrinsic hepatotoxicity, is metabolized to smaller peptides or amino acids by many cells, and does not affect the hepatic drug metabolizing enzymes or transporting molecules.</p></div><div id="Daratumumab.Outcome_and_Management"><h3>Outcome and Management</h3><p>The liver injury attributed to daratumumab has invariably been self-limited and not associated with symptoms or jaundice. There is no information on possible cross sensitivity to the injury among different monoclonal antibodies or therapies directed at epidermal growth factor receptors.</p><p>Drug Class: <a href="/books/n/livertox/AntineoplasticAgents/?report=reader">Antineoplastic Agents</a>, <a href="/books/n/livertox/MonoclonalAntibodies/?report=reader">Monoclonal Antibodies</a></p></div></div><div id="Daratumumab.PRODUCT_INFORMATION"><h2 id="_Daratumumab_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><div id="Daratumumab.BPI" class="box boxed-text-box whole_rhythm hide-overflow"><p>
|
|
<b>REPRESENTATIVE TRADE NAMES</b>
|
|
</p><p>Daratumumab – Darzalex®</p><p>
|
|
<b>DRUG CLASS</b>
|
|
</p><p>Antineoplastic Agents</p><p>
|
|
<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Daratumumab" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COMPLETE LABELING</a>
|
|
</p><p>Product labeling at DailyMed, National Library of Medicine, NIH</p></div></div><div id="Daratumumab.CHEMICAL_FORMULA_AND_STRUCTU"><h2 id="_Daratumumab_CHEMICAL_FORMULA_AND_STRUCTU_">CHEMICAL FORMULA AND STRUCTURE</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figDaratumumabT1"><a href="/books/NBK548759/table/Daratumumab.T1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobDaratumumabT1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="Daratumumab.T1"><a href="/books/NBK548759/table/Daratumumab.T1/?report=objectonly" target="object" rid-ob="figobDaratumumabT1">Table</a></h4></div></div></div><div id="Daratumumab.ANNOTATED_BIBLIOGRAPHY"><h2 id="_Daratumumab_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 25 May 2017</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Daratumumab.R1">Zimmerman HJ. Hepatotoxic effects of oncotherapeutic and immunosuppressive agents. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 673-708.<div><i>(Expert review of hepatotoxicity published in 1999, well before the availability of most monoclonal antibody therapies).</i></div></div></li><li><div class="bk_ref" id="Daratumumab.R2">Reuben A. Hepatotoxicity of immunosuppressive drugs. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2011, pp. 569-91.<div><i>(Review of hepatotoxicity of immunosuppressive drugs; mentions that "the biological immunosuppressants are largely free from hepatotoxicity, with the exception of the TNF alpha antagonists").</i></div></div></li><li><div class="bk_ref" id="Daratumumab.R3">Chabner BA, Barnes J, Neal J, Olson E, Mujagiv H, Sequist L, Wilson W, et al. Targeted therapies: tyrosine kinase inhibitors, monoclonal antibodies, and cytokines. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1731-53.<div><i>(Textbook of pharmacology and therapeutics).</i></div></div></li><li><div class="bk_ref" id="Daratumumab.R4">Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, Minnema MC, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med 2015; 373: 1207-19.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/26308596" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26308596</span></a>]<div><i>(Among 72 patients with refractory multiple myeloma treated with daratumumab [8 vs 16 mg/kg] for up to 24 months, the overall response rate was 25%, and side effects were frequent, with serious adverse events in 40% vs 33%; no mention of ALT elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="Daratumumab.R5">Usmani SZ, Weiss BM, Plesner T, Bahlis NJ, Belch A, Lonial S, Lokhorst HM, et al. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood 2016; 128: 37-44.
|
|
[<a href="/pmc/articles/PMC4937359/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4937359</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27216216" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27216216</span></a>]<div><i>(Among 148 patients with refractory multiple myeloma treated with daratumumab, the overall response rate was 31% and adverse events included fatigue [42%], nausea [30%], anemia [28%], back pain [27%], cough [26%], thrombocytopenia [22%] and neutropenia [21%]; no mention of ALT elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="Daratumumab.R6">Plesner T, Arkenau HT, Gimsing P, Krejcik J, Lemech C, Minnema MC, Lassen U, et al. Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Blood 2016; 128 (14): 1821-8.
|
|
[<a href="/pmc/articles/PMC5054695/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5054695</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27531679" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27531679</span></a>]<div><i>(Phase 1 studies of daratumumab identified no dose limiting toxicities, and phase 2 studies showed that common side effects included neutropenia, thrombocytopenia, cough, diarrhea and fatigue; ALT elevations above 5 times ULN occurred in 1 patient who was also taking lenalidomide and the abnormalities resolved with its dose adjustment).</i></div></div></li><li><div class="bk_ref" id="Daratumumab.R7">Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, et al.; POLLUX Investigators. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 2016; 375: 1319-31.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/27705267" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27705267</span></a>]<div><i>(Among 569 patients with previously treated multiple myeloma treated with lenalidomide and dexamethasone, progression-free survival was prolonged by addition of daratumumab [83% vs 60% at one year], while side effects were more common and included neutropenia, diarrhea, upper respiratory infection and cough; no mention of ALT elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="Daratumumab.R8">Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, et al.; CASTOR Investigators. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med 2016; 375: 754-66.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/27557302" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27557302</span></a>]<div><i>(Among 498 patients with relapsed or refractory multiple myeloma treated with bortezomib and dexamethasone, progression-free survival was increased by the addition of daratumumab [61% vs 27%], and side effects were also greater including thrombocytopenia, neutropenia, peripheral neuropathy, diarrhea, cough and dyspnea; no mention of ALT elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="Daratumumab.R9">Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, Belch A, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet 2016; 387 (10027): 1551-60.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/26778538" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26778538</span></a>]<div><i>(Among 106 patients with refractory multiple myeloma treated with daratumumab, the overall response rate was 29% and adverse events included neutropenia, diarrhea, fatigue, nausea, anemia, thrombocytopenia, back pain and cough; no mention of ALT elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="Daratumumab.R10">Rajkumar SV. Daratumumab in multiple myeloma. Lancet 2016; 387 (10027): 1490-2.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/26778537" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26778537</span></a>]<div><i>(Editorial in response to Lonial [2016] pointing out the improving results of chemotherapy of multiple myeloma, particularly with using combinations of 2 or 3 agents).</i></div></div></li><li><div class="bk_ref" id="Daratumumab.R11">Three new drugs for multiple myeloma. Med Lett Drugs Ther 2016; 58 (1495): e70-1.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/27192621" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27192621</span></a>]<div><i>(Concise review of three agents that had been recently approved for use in multiple myeloma including daratumumab; no mention of ALT elevations or hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="Daratumumab.R12">Brioli A, Mügge LO, Hochhaus A, Von Lilienfeld-Toal M. Safety issues and management of toxicities associated with new treatments for multiple myeloma. Expert Rev Hematol 2017; 10: 193-205.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28116920" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28116920</span></a>]<div><i>(Review of adverse events from new treatments of multiple myeloma and their management; does not specifically discuss hepatotoxicity).</i></div></div></li><li><div class="bk_ref" id="Daratumumab.R13">Kapoor P, Rajkumar SV. Multiple myeloma in 2016: Fresh perspectives on treatment and moments of clarity. Nat Rev Clin Oncol 2017; 14: 73-4.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28071678" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28071678</span></a>]<div><i>(Review of new agents for therapy of multiple myeloma, focusing upon the advantages of triple therapy).</i></div></div></li></ul></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK548759_pubdet_">Publication Details</h2><h3>Publication History</h3><p class="small">Last Update: <span itemprop="dateModified">May 25, 2017</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="https://www.niddk.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Institute of Diabetes and Digestive and Kidney Diseases</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Daratumumab. [Updated 2017 May 25].<span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/livertox/Daptomycin/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/livertox/Daridorexant/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="boxed-text" id="figobDaratumumabBPI"><div id="Daratumumab.BPI" class="box boxed-text-box whole_rhythm hide-overflow"><p>
|
|
<b>REPRESENTATIVE TRADE NAMES</b>
|
|
</p><p>Daratumumab – Darzalex®</p><p>
|
|
<b>DRUG CLASS</b>
|
|
</p><p>Antineoplastic Agents</p><p>
|
|
<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Daratumumab" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COMPLETE LABELING</a>
|
|
</p><p>Product labeling at DailyMed, National Library of Medicine, NIH</p></div></article><article data-type="table-wrap" id="figobDaratumumabT1"><div id="Daratumumab.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548759/table/Daratumumab.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Daratumumab.T1_lrgtbl__"><table><thead><tr><th id="hd_h_Daratumumab.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">DRUG</th><th id="hd_h_Daratumumab.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">CAS REGISTRY NO</th><th id="hd_h_Daratumumab.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">MOLECULAR FORMULA</th><th id="hd_h_Daratumumab.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">STRUCTURE</th></tr></thead><tbody><tr><td headers="hd_h_Daratumumab.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Daratumumab</td><td headers="hd_h_Daratumumab.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://pubchem.ncbi.nlm.nih.gov/substance/135304352" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">945721-28-8</a>
|
|
</td><td headers="hd_h_Daratumumab.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Monoclonal Antibody</td><td headers="hd_h_Daratumumab.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Not Available</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
|
|
|
|
|
|
|
|
|
|
<!-- Book content -->
|
|
|
|
<script type="text/javascript" src="/portal/portal3rc.fcgi/rlib/js/InstrumentNCBIBaseJS/InstrumentPageStarterJS.js"> </script>
|
|
|
|
|
|
<!-- CE8B5AF87C7FFCB1_0191SID /projects/books/PBooks@9.11 portal104 v4.1.r689238 Tue, Oct 22 2024 16:10:51 -->
|
|
<span id="portal-csrf-token" style="display:none" data-token="CE8B5AF87C7FFCB1_0191SID"></span>
|
|
|
|
<script type="text/javascript" src="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/js/3968615.js" snapshot="books"></script></body>
|
|
</html>
|