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class="c-facetbox"><summary class="c-facetbox__summary"><span id="facetbox6">Journal</span></summary><fieldset aria-labelledby="facetbox6"><ul class="c-checkbox"></ul></fieldset></details><details class="c-facetbox"><summary class="c-facetbox__summary"><span id="facetbox7">Discipline</span></summary><fieldset aria-labelledby="facetbox7"><ul class="c-checkbox"></ul></fieldset></details><details class="c-facetbox"><summary class="c-facetbox__summary"><span id="facetbox8">Reuse License</span></summary><fieldset aria-labelledby="facetbox8"><ul class="c-checkbox"></ul></fieldset></details></div></div><button type="submit" id="facet-form-submit" style="display:none">Search</button></div></aside><main id="maincontent"><section class="o-columnbox1"><header><h2 class="o-columnbox1__heading" aria-live="polite">Scholarly Works (2 results)</h2></header><section class="c-scholworks"><div class="c-scholworks__main-column"><ul class="c-scholworks__tag-list"><li class="c-scholworks__tag-article">Article</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/3dx8v2br"><div class="c-clientmarkup">The effect of novel therapies in high-molecular-risk multiple myeloma.</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3ALancman%2C%20Guido">Lancman, Guido</a>; </li><li><a href="/search/?q=author%3ATremblay%2C%20Douglas">Tremblay, Douglas</a>; </li><li><a href="/search/?q=author%3ABarley%2C%20Kevin">Barley, Kevin</a>; </li><li><a href="/search/?q=author%3ABarlogie%2C%20Bart">Barlogie, Bart</a>; </li><li><a href="/search/?q=author%3ACho%2C%20Hearn">Cho, Hearn</a>; </li><li><a href="/search/?q=author%3AJagannath%2C%20Sundar">Jagannath, Sundar</a>; </li><li><a href="/search/?q=author%3AMadduri%2C%20Deepu">Madduri, Deepu</a>; </li><li><a href="/search/?q=author%3AMoshier%2C%20Erin">Moshier, Erin</a>; </li><li><a href="/search/?q=author%3AParekh%2C%20Samir">Parekh, Samir</a>; </li><li class="c-authorlist__end"><a href="/search/?q=author%3AChari%2C%20Ajai">Chari, Ajai</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/ucsf_postprints">UC San Francisco Previously Published Works</a> (2017)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup">Multiple myeloma is a heterogeneous disease with a prognosis that varies with patient factors, disease burden, tumor biology, and treatments. Certain molecular abnormalities confer a worse prognosis and thus are considered high-risk. These include t(4;14), del(17p), t(14;16), t(14;20), hypodiploidy, and gain(1q)/del(1p). In our previous review in 2013, we discussed the effect of available therapies on prognosis in these high-risk patients. Since then, seven phase 3 clinical trials in relapsed myeloma with 1 to 3 lines of therapy have been conducted, resulting in the approval of panobinostat, ixazomib, daratumumab, and elotuzumab, as well as additional data on carfilzomib. In our current review of these studies, all the novel therapies resulted in an improvement in progression-free survival for high-risk patients, but none of the trials provided clear statistical evidence that they overcame high-risk status. Moreover, there are several limitations in the currently available data. For example, the patients Revised International Staging System score is generally not reported, and even when it is reported, it is usually at the time of initial diagnosis rather than at the time of study entry. Furthermore, the methodology used to determine risk suffers from technologic issues. Finally, the clonal and allele burden and concurrent molecular abnormalities can affect risk status and prognosis. To determine the optimal therapy for high-risk patients, future clinical trials should provide standardized risk assessments for all patients in addition to hazard ratios for Kaplan-Meier survival curves of high-risk patients vs those of standard-risk patients to determine if high-risk status has truly been overcome by a novel agent.</div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/3dx8v2br"><img src="/cms-assets/4ad133215437bf43c3e3e6d0520d9d6f3a23295c3f395979a8940b5bc7cdce2b" alt="Cover page: The effect of novel therapies in high-molecular-risk multiple myeloma."/></a></div></section><section class="c-scholworks"><div class="c-scholworks__main-column"><ul class="c-scholworks__tag-list"><li class="c-scholworks__tag-article">Article</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/0hb1560d"><div class="c-clientmarkup">Anagrelide for platelet-directed cytoreduction in polycythemia vera: Insights into utility and safety outcomes from a large multi-center database.</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3ARippel%2C%20Noa">Rippel, Noa</a>; </li><li><a href="/search/?q=author%3ATremblay%2C%20Douglas">Tremblay, Douglas</a>; </li><li><a href="/search/?q=author%3AZubizarreta%2C%20Nicole">Zubizarreta, Nicole</a>; </li><li><a href="/search/?q=author%3APodoltsev%2C%20Nikolai">Podoltsev, Nikolai</a>; </li><li><a href="/search/?q=author%3AGotlib%2C%20Jason">Gotlib, Jason</a>; </li><li><a href="/search/?q=author%3AHeaney%2C%20Mark">Heaney, Mark</a>; </li><li><a href="/search/?q=author%3AKuykendall%2C%20Andrew">Kuykendall, Andrew</a>; </li><li><a href="/search/?q=author%3AOConnell%2C%20Casey">OConnell, Casey</a>; </li><li><a href="/search/?q=author%3AShammo%2C%20Jamile">Shammo, Jamile</a>; </li><li><a href="/search/?q=author%3AFleischman%2C%20Angela">Fleischman, Angela</a>; </li><li><a href="/search/?q=author%3AKremyanskaya%2C%20Marina">Kremyanskaya, Marina</a>; </li><li><a href="/search/?q=author%3AHoffman%2C%20Ronald">Hoffman, Ronald</a>; </li><li><a href="/search/?q=author%3AMesa%2C%20Ruben">Mesa, Ruben</a>; </li><li><a href="/search/?q=author%3AYacoub%2C%20Abdulraheem">Yacoub, Abdulraheem</a>; </li><li class="c-authorlist__end"><a href="/search/?q=author%3AMascarenhas%2C%20John">Mascarenhas, John</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/uci_postprints">UC Irvine Previously Published Works</a> (2022)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup">Anagrelide (ANA) is a platelet-specific cytoreductive agent utilized in the guideline-directed management of high-risk essential thrombocythemia. In the context of polycythemia vera (PV), ANA is occasionally employed in clinical practice, although data has not consistently demonstrated a benefit to targeting a platelet goal as a therapeutic endpoint. The aim of the current study was to delineate the patterns of ANA use in PV, and to describe outcomes and toxicities. Within a multi-center cohort of 527 patients with PV, 48 received ANA (9 excluded for absent data). 27 (69.2%) had high-risk PV, 10 (25.6%) had prior thrombosis, and none had extreme thrombocytosis, acquired von Willebrand disease, and/or documented resistance to hydroxyurea. While ANA effectively lowered median platelet count, 43.5% of patients had an unresolved thrombocytosis at time of ANA discontinuation. Treatment-emergent adverse events-including headaches, cardiac palpitations and arrhythmias, nausea, vomiting and/or diarrhea-led to ANA discontinuation in 76.9% of patients. Further, three patients experienced arterial thromboses during a median duration of 27.5 months of ANA therapy. In conclusion, this study highlights ANAs restrictive tolerability profile which, compounded by the absence of clear advantage to strict platelet control in PV, suggests the use of ANA should be limited in this setting.</div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/0hb1560d"><img src="/cms-assets/123bdfa64d3987d6cad45612fd7b3cb1c298ced275c335828d8c0433d03151c6" alt="Cover page: Anagrelide for platelet-directed cytoreduction in polycythemia vera: Insights into utility and safety outcomes from a large multi-center database."/></a></div></section></section></main></form></div><div><div class="c-toplink"><a href="javascript:window.scrollTo(0, 0)">Top</a></div><footer class="c-footer"><nav class="c-footer__nav"><ul><li><a href="/">Home</a></li><li><a href="/aboutEschol">About eScholarship</a></li><li><a href="/campuses">Campus Sites</a></li><li><a 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Certain molecular abnormalities confer a worse prognosis and thus are considered high-risk. These include t(4;14), del(17p), t(14;16), t(14;20), hypodiploidy, and gain(1q)/del(1p). In our previous review in 2013, we discussed the effect of available therapies on prognosis in these high-risk patients. Since then, seven phase 3 clinical trials in relapsed myeloma with 1 to 3 lines of therapy have been conducted, resulting in the approval of panobinostat, ixazomib, daratumumab, and elotuzumab, as well as additional data on carfilzomib. In our current review of these studies, all the novel therapies resulted in an improvement in progression-free survival for high-risk patients, but none of the trials provided clear statistical evidence that they overcame high-risk status. Moreover, there are several limitations in the currently available data. For example, the patients Revised International Staging System score is generally not reported, and even when it is reported, it is usually at the time of initial diagnosis rather than at the time of study entry. Furthermore, the methodology used to determine risk suffers from technologic issues. Finally, the clonal and allele burden and concurrent molecular abnormalities can affect risk status and prognosis. To determine the optimal therapy for high-risk patients, future clinical trials should provide standardized risk assessments for all patients in addition to hazard ratios for Kaplan-Meier survival curves of high-risk patients vs those of standard-risk patients to determine if high-risk status has truly been overcome by a novel agent.","content_type":"application/pdf","author_hide":null,"authors":[{"name":"Lancman, Guido","fname":"Guido","lname":"Lancman"},{"name":"Tremblay, Douglas","fname":"Douglas","lname":"Tremblay"},{"name":"Barley, Kevin","fname":"Kevin","lname":"Barley"},{"name":"Barlogie, Bart","fname":"Bart","lname":"Barlogie"},{"name":"Cho, Hearn","fname":"Hearn","lname":"Cho"},{"name":"Jagannath, Sundar","fname":"Sundar","lname":"Jagannath"},{"name":"Madduri, Deepu","fname":"Deepu","lname":"Madduri"},{"name":"Moshier, Erin","fname":"Erin","lname":"Moshier"},{"name":"Parekh, Samir","fname":"Samir","lname":"Parekh"},{"name":"Chari, Ajai","fname":"Ajai","lname":"Chari"}],"supp_files":[{"type":"pdf","count":0},{"type":"image","count":0},{"type":"video","count":0},{"type":"audio","count":0},{"type":"zip","count":0},{"type":"other","count":0}],"thumbnail":{"width":121,"height":156,"asset_id":"4ad133215437bf43c3e3e6d0520d9d6f3a23295c3f395979a8940b5bc7cdce2b","timestamp":1725057308,"image_type":"png"},"pub_year":2017,"genre":"article","rights":null,"peerReviewed":true,"unitInfo":{"displayName":"UC San Francisco Previously Published Works","link_path":"ucsf_postprints"}},{"id":"qt0hb1560d","title":"Anagrelide for platelet-directed cytoreduction in polycythemia vera: Insights into utility and safety outcomes from a large multi-center database.","abstract":"Anagrelide (ANA) is a platelet-specific cytoreductive agent utilized in the guideline-directed management of high-risk essential thrombocythemia. In the context of polycythemia vera (PV), ANA is occasionally employed in clinical practice, although data has not consistently demonstrated a benefit to targeting a platelet goal as a therapeutic endpoint. The aim of the current study was to delineate the patterns of ANA use in PV, and to describe outcomes and toxicities. Within a multi-center cohort of 527 patients with PV, 48 received ANA (9 excluded for absent data). 27 (69.2%) had high-risk PV, 10 (25.6%) had prior thrombosis, and none had extreme thrombocytosis, acquired von Willebrand disease, and/or documented resistance to hydroxyurea. While ANA effectively lowered median platelet count, 43.5% of patients had an unresolved thrombocytosis at time of ANA discontinuation. Treatment-emergent adverse events-including headaches, cardiac palpitations and arrhythmias, nausea, vomiting and/or diarrhea-led to ANA discontinuation in 76.9% of patients. Further, three patients experienced arterial thromboses during a median duration of 27.5 months of ANA therapy. In conclusion, this study highlights ANAs restrictive tolerability profile which, compounded by the absence of clear advantage to strict platelet control in PV, suggests the use of ANA should be limited in this setting.","content_type":"application/pdf","author_hide":null,"authors":[{"name":"Rippel, Noa","fname":"Noa","lname":"Rippel"},{"name":"Tremblay, Douglas","fname":"Douglas","lname":"Tremblay"},{"name":"Zubizarreta, Nicole","fname":"Nicole","lname":"Zubizarreta"},{"name":"Podoltsev, Nikolai","fname":"Nikolai","lname":"Podoltsev"},{"name":"Gotlib, Jason","fname":"Jason","lname":"Gotlib"},{"name":"Heaney, Mark","fname":"Mark","lname":"Heaney"},{"name":"Kuykendall, Andrew","fname":"Andrew","lname":"Kuykendall"},{"name":"OConnell, Casey","fname":"Casey","lname":"OConnell"},{"name":"Shammo, Jamile","fname":"Jamile","lname":"Shammo"},{"name":"Fleischman, Angela","email":"agf@uci.edu","fname":"Angela","lname":"Fleischman"},{"name":"Kremyanskaya, Marina","fname":"Marina","lname":"Kremyanskaya"},{"name":"Hoffman, Ronald","fname":"Ronald","lname":"Hoffman"},{"name":"Mesa, Ruben","fname":"Ruben","lname":"Mesa"},{"name":"Yacoub, Abdulraheem","fname":"Abdulraheem","lname":"Yacoub"},{"name":"Mascarenhas, John","fname":"John","lname":"Mascarenhas"}],"supp_files":[{"type":"pdf","count":0},{"type":"image","count":0},{"type":"video","count":0},{"type":"audio","count":0},{"type":"zip","count":0},{"type":"other","count":0}],"thumbnail":{"width":121,"height":150,"asset_id":"123bdfa64d3987d6cad45612fd7b3cb1c298ced275c335828d8c0433d03151c6","timestamp":1732979627,"image_type":"png"},"pub_year":2022,"genre":"article","rights":null,"peerReviewed":true,"unitInfo":{"displayName":"UC Irvine Previously Published Works","link_path":"uci_postprints"}}],"facets":[{"display":"Type of Work","fieldName":"type_of_work","facets":[{"value":"article","count":2,"displayName":"Article"},{"value":"monograph","count":0,"displayName":"Book"},{"value":"dissertation","count":0,"displayName":"Theses"},{"value":"multimedia","count":0,"displayName":"Multimedia"}]},{"display":"Peer Review","fieldName":"peer_reviewed","facets":[{"value":"1","count":2,"displayName":"Peer-reviewed only"}]},{"display":"Supplemental Material","fieldName":"supp_file_types","facets":[{"value":"video","count":0,"displayName":"Video"},{"value":"audio","count":0,"displayName":"Audio"},{"value":"images","count":0,"displayName":"Images"},{"value":"zip","count":0,"displayName":"Zip"},{"value":"other files","count":0,"displayName":"Other files"}]},{"display":"Publication Year","fieldName":"pub_year","range":{"pub_year_start":null,"pub_year_end":null}},{"display":"Campus","fieldName":"campuses","facets":[{"value":"ucb","count":0,"displayName":"UC Berkeley"},{"value":"ucd","count":0,"displayName":"UC Davis"},{"value":"uci","count":1,"displayName":"UC Irvine"},{"value":"ucla","count":0,"displayName":"UCLA"},{"value":"ucm","count":0,"displayName":"UC Merced"},{"value":"ucr","count":0,"displayName":"UC Riverside"},{"value":"ucsd","count":0,"displayName":"UC San Diego"},{"value":"ucsf","count":1,"displayName":"UCSF"},{"value":"ucsb","count":0,"displayName":"UC Santa Barbara"},{"value":"ucsc","count":0,"displayName":"UC Santa Cruz"},{"value":"ucop","count":0,"displayName":"UC Office of the President"},{"value":"lbnl","count":0,"displayName":"Lawrence Berkeley National Laboratory"},{"value":"anrcs","count":0,"displayName":"UC Agriculture & Natural Resources"}]},{"display":"Department","fieldName":"departments","facets":[{"value":"ucideptmed","count":1,"displayName":"UC Irvine Department of Medicine"}]},{"display":"Journal","fieldName":"journals","facets":[]},{"display":"Discipline","fieldName":"disciplines","facets":[]},{"display":"Reuse License","fieldName":"rights","facets":[]}]};</script> <script src="/js/vendors~app-bundle-7424603c338d723fd773.js"></script> <script src="/js/app-bundle-8362e6d7829414ab4baa.js"></script> </body> </html>