{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:58:57Z","timestamp":1790521137570,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T00:00:00Z","timestamp":1579132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Safety profiles of oral PI3K inhibitors have resulted in US FDA black box warnings regarding fatal\/serious toxicities. The approved intravenous PI3K inhibitor copanlisib has low incidence of severe toxicities and no black box warnings, but chronic treatment effects were unknown. We provide an update on safety and efficacy of copanlisib with a minimum 2\u2010year follow\u2010up of the CHRONOS\u20101 study. A total of 142 patients with histologically confirmed indolent B\u2010cell lymphoma who had relapsed after or were refractory to \u22652 prior treatments received intravenous copanlisib 60\u2009mg on days 1, 8, and 15 (28\u2010day\u2009cycle). The primary efficacy endpoint was objective response rate (ORR) after \u22654 cycles (independent assessment). The predominant histology was follicular lymphoma (n = 104). The ORR was 60.6% (seven additional complete responses since primary analysis). Secondary endpoints of median duration of response, progression\u2010free survival, and overall survival were 14.1 months (median follow\u2010up, 16.1 months), 12.5 months (median follow\u2010up, 14.0 months), and 42.6 months (median follow\u2010up, 31.5 months), respectively. Median safety follow\u2010up was 6.7 months; 26% of patients received treatment for &gt;1 year. Common treatment\u2010emergent adverse events (TEAEs) (all grade\/grade 3\/grade 4) were transient hyperglycemia (50.0%\/33.1%\/7.0%), diarrhea (35.2%\/8.5%\/0%), transient hypertension (29.6%\/23.9%\/0%), and neutropenia (28.9%\/9.2%\/14.8%). Serious AEs were largely unchanged, with no new cases of pneumonitis (4.2%), diarrhea (2.8%), or grade 5 events. Note, TEAEs showed no evidence for increased incidence or worsening following longer exposure in patients treated &gt;1 year. Long\u2010term follow\u2010up of patients with relapsed\/refractory indolent B\u2010cell lymphoma treated with intravenous copanlisib demonstrated durable, enhanced responses without evidence of worsening TEAEs, as reported for orally administered PI3K inhibitors.<\/jats:p>","DOI":"10.1002\/ajh.25711","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T11:55:26Z","timestamp":1577102126000},"page":"362-371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":130,"title":["Long\u2010term safety and efficacy of the PI3K inhibitor copanlisib in patients with relapsed or refractory indolent lymphoma: 2\u2010year follow\u2010up of the CHRONOS\u20101 study"],"prefix":"10.1002","volume":"95","author":[{"given":"Martin","family":"Dreyling","sequence":"first","affiliation":[{"name":"Department of Medicine III University Hospital, LMU  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Santoro","sequence":"additional","affiliation":[{"name":"Humanitas Clinical and Research Center  Rozzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigina","family":"Mollica","sequence":"additional","affiliation":[{"name":"Maisonneuve\u2010Rosemont Hospital Research Centre  Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirpa","family":"Lepp\u00e4","sequence":"additional","affiliation":[{"name":"Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Follows","sequence":"additional","affiliation":[{"name":"Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Lenz","sequence":"additional","affiliation":[{"name":"Translational Oncology University Hospital M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Seog","family":"Kim","sequence":"additional","affiliation":[{"name":"Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnon","family":"Nagler","sequence":"additional","affiliation":[{"name":"Chaim Sheba Medical Center Tel Aviv University, Tel HaShomer  Tel Aviv\u2010Yafo Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Dimou","sequence":"additional","affiliation":[{"name":"School of Medicine National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Demeter","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhit","family":"\u00d6zcan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology, Ankara University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Kosinova","sequence":"additional","affiliation":[{"name":"Kemerovo Regional Clinical Hospital  Kemerovo Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krimo","family":"Bouabdallah","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Hospital of Bordeaux, H\u00f4pital Haut\u2010L\u00e9v\u00eaque  Pessac France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Morschhauser","sequence":"additional","affiliation":[{"name":"Univ. Lille, CHU Lille, EA 7365 \u2010 GRITA \u2010 Groupe de Recherche sur les formes Injectables et les Technologies Associ\u00e9es  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don A.","family":"Stevens","sequence":"additional","affiliation":[{"name":"Norton Cancer Institute  Louisville Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Trevarthen","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Care and Research Institute of Colorado, LLC  Englewood Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Munoz","sequence":"additional","affiliation":[{"name":"Banner MD Anderson Cancer Center Clinic  Gilbert Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liana","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Bayer SA  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Hiemeyer","sequence":"additional","affiliation":[{"name":"Pharmaceutical Division Bayer AG  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Miriyala","sequence":"additional","affiliation":[{"name":"Bayer HealthCare Pharmaceuticals, Inc.  Whippany New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Garcia\u2010Vargas","sequence":"additional","affiliation":[{"name":"Bayer HealthCare Pharmaceuticals, Inc.  Whippany New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barrett H.","family":"Childs","sequence":"additional","affiliation":[{"name":"Bayer HealthCare Pharmaceuticals, Inc.  Whippany New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2112-2651","authenticated-orcid":false,"given":"Pier Luigi","family":"Zinzani","sequence":"additional","affiliation":[{"name":"Institute of Hematology \u201cSer\u00e0gnoli\u201d, University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw400"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.75.4648"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.105"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-1814"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314583"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.00915"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2012.12.002"},{"issue":"11","key":"e_1_2_8_9_1","first-page":"821","article-title":"PI3K inhibitors: understanding toxicity mechanisms and management","volume":"31","author":"Greenwell IB","year":"2017","journal-title":"Oncology (Williston Park)"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000522"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2015.1022770"},{"key":"e_1_2_8_12_1","unstructured":"US Food and Drug Administration. COPIKTRA (duvelisib) highlights of prescribing information;2018.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/211155s000lbl.pdf. Accessed September 9 2019."},{"key":"e_1_2_8_13_1","unstructured":"US Food and Drug Administration. ZYDELIG (idelalisib) highlights of prescribing information;2014.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2014\/206545lbl.pdf. Accessed September 9 2019."},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-12-0993-T"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201600148"},{"key":"e_1_2_8_16_1","unstructured":"US Food and Drug Administration. ALIQOPA (copanlisib) highlights of prescribing information;2017. Available from:https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/209936s000lbl.pdf. Accessed Septemzber 9 2019."},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.2403"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3816\/CLML.2011.n.010"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(96)00075-X"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V124.21.1708.1708"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30082-2"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.169656"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx289"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw282"},{"issue":"8","key":"e_1_2_8_25_1","article-title":"BYL719, a next generation PI3K alpha specific inhibitor: preliminary safety, PK, and efficacy results from the first\u2010in\u2010human study","volume":"72","author":"Juric D","year":"2012","journal-title":"Cancer Res"},{"issue":"8","key":"e_1_2_8_26_1","article-title":"GDC\u20100032, a beta isoform\u2010sparing PI3K inhibitor: results of a first\u2010in\u2010human phase Ia dose escalation study","volume":"73","author":"Juric D","year":"2013","journal-title":"Cancer Res."},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0134"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.03.035"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1813904"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-19-0466"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25228"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.25711","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.25711","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajh.25711","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.25711","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T18:22:41Z","timestamp":1693678961000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.25711"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,16]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.1002\/ajh.25711"],"URL":"https:\/\/doi.org\/10.1002\/ajh.25711","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,16]]},"assertion":[{"value":"2019-12-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}