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We evaluated the efficacy and safety of the phosphatidylinositol 3-kinase inhibitor copanlisib in patients with relapsed\/refractory DLBCL and assessed the relationship between efficacy and DLBCL cell of origin (COO; activated B-cell like [ABC] and germinal center B-cell like [GCB]) and other biomarkers. The primary endpoint was objective response rate (ORR) in DLBCL COO subgroups (ABC, GCB, and unclassifiable) and by <jats:italic>CD79B<\/jats:italic> mutational status (NCT02391116). Sixty-seven patients received copanlisib (ABC DLBCL, <jats:italic>n<\/jats:italic>\u2009=\u200919; GCB DLBCL, <jats:italic>n<\/jats:italic>\u2009=\u200930; unclassifiable, <jats:italic>n<\/jats:italic>\u2009=\u20093; missing, <jats:italic>n<\/jats:italic>\u2009=\u200915). The ORR was 19.4%; 31.6% and 13.3% in ABC and GCB DLBCL patients, respectively. ORR was 22.2%\/20.0% for patients with\/without <jats:italic>CD79B<\/jats:italic> mutations (wild type, <jats:italic>n<\/jats:italic>\u2009=\u200945; mutant, <jats:italic>n<\/jats:italic>\u2009=\u20099; missing, <jats:italic>n<\/jats:italic>\u2009=\u200913). Overall median progression-free survival and duration of response were 1.8 and 4.3 months, respectively. Adverse events included hypertension (40.3%), diarrhea (37.3%), and hyperglycemia (32.8%). Aberrations were detected in 338 genes, including <jats:italic>BCL2<\/jats:italic> (53.7%) and <jats:italic>MLL2<\/jats:italic> (53.7%). A 16-gene signature separating responders from nonresponders was identified. Copanlisib treatment demonstrated a manageable safety profile in patients with relapsed\/refractory DLBCL and a numerically higher response rate in ABC vs. GCB DLBCL patients.<\/jats:p>","DOI":"10.1038\/s41375-020-0743-y","type":"journal-article","created":{"date-parts":[[2020,2,15]],"date-time":"2020-02-15T01:02:35Z","timestamp":1581728555000},"page":"2184-2197","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma"],"prefix":"10.1038","volume":"34","author":[{"given":"Georg","family":"Lenz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliza","family":"Hawkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Verhoef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Haioun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soon","family":"Thye Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae","family":"Seog Heo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirit","family":"Ardeshna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"Chong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Haaber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Gorbatchevsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Lippert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Hiemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Piraino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Beckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Pe\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoriya","family":"Buvaylo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barrett H.","family":"Childs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9541-8666","authenticated-orcid":false,"given":"Gilles","family":"Salles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,14]]},"reference":[{"key":"743_CR1","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1200\/JCO.2010.33.3252","volume":"29","author":"H Nogai","year":"2011","unstructured":"Nogai H, D\u00f6rken B, Lenz G. 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EH has participated in a consulting or advisory role for Bristol-Myers Squibb, Celgene, and Janssen, has been on a speaker\u2019s bureau for Bristol-Myers Squibb, Janssen, and Roche, has received research funding from Bristol-Myers Squibb, Celgene, Merck Serono, and Merck Sharp & Dohme, and has had travel, accommodation, and expenses reimbursed by Bristol-Myers Squibb, Roche, and Takeda. CH has received honoraria from Celgene, Gilead, Janssen, Novartis, Roche, and Takeda, has participated in a consulting or advisory role for Celgene, Gilead, Janssen, Roche, and Takeda, and has had travel, accommodation, and expenses reimbursed by Celgene and Roche. KA has received honoraria from Takeda, has participated in a consulting or advisory role for Celgene, Gilead, Roche, and Takeda, has received research funding from Cell Medica, Gilead, Infinity, Merck, and Pharmacyclics, has had travel, accommodation, and expenses reimbursed by Celgene, Gilead, Roche, and Takeda, and is supported by the UCLH\/UCL Biomedical Research Centre. GC has received research funding from Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Hutchison, Incyte, Merck Serono, and Novartis. WS is employed by Bayer HealthCare Pharmaceuticals. IG was employed by Bayer HealthCare Pharmaceuticals. SL is employed by, and has stock or other ownership at, Bayer AG. FH is employed by Bayer AG and has stock or other ownership at Bayer AG, Evotec AG, Gilead, Hologen AG, Medigene AG, and 4SC AG. PP is employed by, and has stock or other ownership at, Bayer AG. GB is employed by Bayer AG. CP is employed by, has stock at, and has co-authored patents at Bayer HealthCare Pharmaceuticals. VB is employed by Bayer HealthCare Pharmaceuticals. BHC is employed by Bayer HealthCare Pharmaceuticals. GS has received honoraria from Acerta, Amgen, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Merck, MorphoSys, Novartis, Pfizer, Roche, and Servier, has participated in a consulting or advisory role for Amgen, Celgene, Gilead, Merck, Novartis, Pfizer, Roche, and Servier, has received research funding from Acerta, Amgen, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Merck, MorphoSys, Novartis, Pfizer, Roche, Sanofi, Servier, and Takeda, and has had travel, accommodation, and expenses reimbursed by Roche and Sanofi. GV, STL, DSH, and JH declare no competing financial interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}