{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:14:27Z","timestamp":1792174467330,"version":"4.4.0"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2017,11,30]],"date-time":"2017-11-30T00:00:00Z","timestamp":1512000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title\/>\n                  <jats:p>On August 28, 2015, a marketing authorization valid through the European Union was issued for panobinostat, in combination with bortezomib and dexamethasone, for the treatment of adult patients with relapsed and\/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent (IMiD).<\/jats:p>\n                  <jats:p>Panobinostat is an orally available histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDAC proteins at nanomolar concentrations. HDAC proteins catalyze the removal of acetyl groups from the lysine residues of histones and some nonhistone proteins. Inhibition of HDAC activity results in increased acetylation of histone proteins, an epigenetic alteration that results in a relaxing of chromatin, leading to transcriptional activation. The recommended starting dose of panobinostat is 20 mg, taken orally in a cyclical manner for up to 48 weeks.<\/jats:p>\n                  <jats:p>The use of panobinostat in combination with bortezomib and dexamethasone was studied in a randomized, double-blind, placebo-controlled, multicenter phase III study (PANORAMA I) in 768 patients with relapsed or relapsed and refractory multiple myeloma who had received one to three prior lines of therapies. In the subgroup of patients who have received at least two prior regimens including bortezomib and an IMiD, there was a difference of 7.8 months in the progression-free survival in favor of the experimental arm (12.5 months for panobinostat\u2009+\u2009bortezomib\u2009+\u2009dexamethasone vs. 4.7 months for placebo\u2009+\u2009bortezomib\u2009+\u2009dexamethasone; hazard ratio\u2009=\u20090.47, 95% confidence interal 0.31\u20130.72; log-rank p value\u2009=\u2009.0003). The incidence of grade 3\u20134 adverse events suspected to be related to study drug was 76.9% vs. 51.2%, for the panobinostat and the placebo group, respectively. The most common side effects (grade 3\u20134) associated with panobinostat included diarrhea (18.9%), fatigue (14.7%), nausea (4.5%), vomiting (5.5%), thrombocytopenia (43.6%), anemia (7.9%), neutropenia (16.5%) and lymphopenia (8.1%).<\/jats:p>\n                  <jats:p>This article summarizes the scientific review of the application leading to regulatory approval in the European Union. The full scientific assessment report and product information, including the Summary of Product Characteristics, are available on the European Medicines Agency website (http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/includes\/medicines\/medicines_landing_page.jsp&amp;mid=).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Implications for Practice<\/jats:title>\n                  <jats:p>Farydak was approved in the European Union in combination with bortezomib and dexamethasone, for the treatment of adult patients with relapsed and\/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent (IMiD). The addition of panobinostat to bortezomib and dexamethasone resulted in a clinically meaningful and statistically significant improvement of progression-free survival compared with bortezomib and dexamethasone, and an additional therapeutic option with a new mechanism of action was considered valuable. Although the toxicity associated with panobinostat combination was significant, at the time of the marketing authorization of panobinostat, it was considered that it was acceptable and that it should be left to the clinician and the patient to decide whether the panobinostat combination is the preferred treatment option or not.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2017-0301","type":"journal-article","created":{"date-parts":[[2017,11,30]],"date-time":"2017-11-30T21:05:12Z","timestamp":1512075912000},"page":"631-636","source":"Crossref","is-referenced-by-count":34,"title":["EMA Review of Panobinostat (Farydak) for the Treatment of Adult Patients with Relapsed and\/or Refractory Multiple Myeloma"],"prefix":"10.1093","volume":"23","author":[{"given":"Kyriaki","family":"Tzogani","sequence":"first","affiliation":[{"name":"European Medicines Agency, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"van Hennik","sequence":"additional","affiliation":[{"name":"European Medicines Agency, London, United Kingdom"},{"name":"Medicines Evaluation Board, Den Haag, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ita","family":"Walsh","sequence":"additional","affiliation":[{"name":"European Medicines Agency, London, United Kingdom"},{"name":"Medicines Evaluation Board, Den Haag, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"De Graeff","sequence":"additional","affiliation":[{"name":"European Medicines Agency, London, United Kingdom"},{"name":"Medicines Evaluation Board, Den Haag, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Folin","sequence":"additional","affiliation":[{"name":"European Medicines Agency, London, United Kingdom"},{"name":"L\u00e4kemedelsverket, Medicinal Products Agency, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Sj\u00f6berg","sequence":"additional","affiliation":[{"name":"European Medicines Agency, London, United Kingdom"},{"name":"L\u00e4kemedelsverket, Medicinal Products Agency, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Salmonson","sequence":"additional","affiliation":[{"name":"European Medicines Agency, London, United Kingdom"},{"name":"L\u00e4kemedelsverket, Medicinal Products Agency, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Bergh","sequence":"additional","affiliation":[{"name":"European Medicines Agency, London, United Kingdom"},{"name":"Karolinska Institutet and University Hospital, Radumhemmet, Karolinska Oncology, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Laane","sequence":"additional","affiliation":[{"name":"European Medicines Agency, London, United Kingdom"},{"name":"North Estonia Regional Hospital, Tallinn, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Ludwig","sequence":"additional","affiliation":[{"name":"European Medicines Agency, London, United Kingdom"},{"name":"Wilhelminen Cancer Research Institute, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gisselbrecht","sequence":"additional","affiliation":[{"name":"European Medicines Agency, London, United Kingdom"},{"name":"Hospital Saint Louis, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Pignatti","sequence":"additional","affiliation":[{"name":"European Medicines Agency, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,11,30]]},"reference":[{"key":"2021122510450711700_onco12317-bib-0001","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1056\/NEJMra041875","article-title":"Multiple myeloma","volume":"351","author":"Kyle","year":"2004","journal-title":"N Engl J Med"},{"key":"2021122510450711700_onco12317-bib-0002","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.ejca.2012.12.027","article-title":"Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012","volume":"49","author":"Ferlay","year":"2013","journal-title":"Eur J Cancer"},{"key":"2021122510450711700_onco12317-bib-0003","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4065\/78.1.21","article-title":"Review of 1027 patients with newly diagnosed multiple myeloma","volume":"78","author":"Kyle","year":"2003","journal-title":"Mayo Clin Proc"},{"key":"2021122510450711700_onco12317-bib-0004","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1046\/j.1365-2141.1998.00930.x","article-title":"Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant","volume":"102","author":"Blad\u00e9","year":"1998","journal-title":"Br J Haematol"},{"key":"2021122510450711700_onco12317-bib-0005","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1182\/bloodadvances.2016002493","article-title":"Recent trends in multiple myeloma incidence and survival by age, race, and ethnicity in the United States","volume":"1","author":"Costa","year":"2017","journal-title":"Blood Adv"},{"key":"2021122510450711700_onco12317-bib-0006","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.mayocp.2015.11.007","article-title":"Multiple myeloma: Diagnosis and treatment","volume":"91","author":"Rajkumar","year":"2016","journal-title":"Mayo Clin Proc"},{"key":"2021122510450711700_onco12317-bib-0007","author":"National Comprehensive Cancer Network [NCCN]","year":"2017"},{"key":"2021122510450711700_onco12317-bib-0008","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/leu.2011.196","article-title":"Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: A multicenter international myeloma working group study","volume":"26","author":"Kumar","year":"2012","journal-title":"Leukemia"},{"key":"2021122510450711700_onco12317-bib-0009","doi-asserted-by":"crossref","first-page":"734","DOI":"10.2174\/138161213804581945","article-title":"New insights into the treatment of multiple myeloma with histone deacetylase inhibitors","volume":"19","author":"Cea","year":"2013","journal-title":"Curr Pharm Des"},{"key":"2021122510450711700_onco12317-bib-0010","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/S1470-2045(14)70440-1","article-title":"Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial","volume":"15","author":"San-Miguel","year":"2014","journal-title":"The Lancet Oncology"},{"key":"2021122510450711700_onco12317-bib-0011","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1200\/JCO.2012.46.7068","article-title":"Phase Ib study of panobinostat and bortezomib in relapsed or relapsed and refractory multiple myeloma","volume":"31","author":"San-Miguel","year":"2013","journal-title":"J Clin Oncol"},{"key":"2021122510450711700_onco12317-bib-0012","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1182\/blood-2013-01-481325","article-title":"PANORAMA 2: Panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma","volume":"122","author":"Richardson","year":"2013","journal-title":"Blood"},{"key":"2021122510450711700_onco12317-bib-0013","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1007\/s12185-016-2008-0","article-title":"Histone deacetylase inhibitors in multiple myeloma: From bench to bedside","volume":"104","author":"Harada","year":"2016","journal-title":"Int J Hematol"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1634\/theoncologist.2017-0301","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1634\/theoncologist.2017-0301","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/23\/5\/631\/41915480\/oncolo_23_5_631.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/23\/5\/631\/41915480\/oncolo_23_5_631.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,25]],"date-time":"2021-12-25T10:47:44Z","timestamp":1640429264000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/23\/5\/631\/6439591"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,30]]},"references-count":13,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2017,11,30]]},"published-print":{"date-parts":[[2018,5,1]]}},"URL":"https:\/\/doi.org\/10.1634\/theoncologist.2017-0301","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,5,1]]},"published":{"date-parts":[[2017,11,30]]}}}