Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma
Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have adverse outcomes. 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 or...
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| Veröffentlicht in: | Leukemia 2020-08, Vol.34 (8), p.2184-2197 |
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| creator | Lenz, Georg Hawkes, Eliza Verhoef, Gregor Haioun, Corinne Thye Lim, Soon Seog Heo, Dae Ardeshna, Kirit Chong, Geoffrey Haaber, Jacob Shi, Wei Gorbatchevsky, Igor Lippert, Susanne Hiemeyer, Florian Piraino, Paolo Beckmann, Georg Peña, Carol Buvaylo, Viktoriya Childs, Barrett H. Salles, Gilles |
| description | Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have adverse outcomes. 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
CD79B
mutational status (NCT02391116). Sixty-seven patients received copanlisib (ABC DLBCL,
n
= 19; GCB DLBCL,
n
= 30; unclassifiable,
n
= 3; missing,
n
= 15). 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
CD79B
mutations (wild type,
n
= 45; mutant,
n
= 9; missing,
n
= 13). 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
BCL2
(53.7%) and
MLL2
(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. |
| doi_str_mv | 10.1038/s41375-020-0743-y |
| format | Article |
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CD79B
mutational status (NCT02391116). Sixty-seven patients received copanlisib (ABC DLBCL,
n
= 19; GCB DLBCL,
n
= 30; unclassifiable,
n
= 3; missing,
n
= 15). 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
CD79B
mutations (wild type,
n
= 45; mutant,
n
= 9; missing,
n
= 13). 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
BCL2
(53.7%) and
MLL2
(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.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/s41375-020-0743-y</identifier><identifier>PMID: 32060403</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>1-Phosphatidylinositol 3-kinase ; 13 ; 13/51 ; 38 ; 38/23 ; 631/67/1059/602 ; 692/699/67/1990/291/1621/1915 ; Adult ; Adverse events ; Aged ; Aged, 80 and over ; B-cell lymphoma ; Biomarkers ; Cancer Research ; Care and treatment ; CD79 Antigens - genetics ; Chief operating officers ; Critical Care Medicine ; Development and progression ; Diarrhea ; Diseases ; Enzyme inhibitors ; Female ; Hematology ; High-Throughput Nucleotide Sequencing ; Humans ; Hyperglycemia ; Hypertension ; Intensive ; Internal Medicine ; Kinases ; Lymphocytes B ; Lymphoma ; Lymphoma, Large B-Cell, Diffuse - drug therapy ; Lymphoma, Large B-Cell, Diffuse - genetics ; Lymphoma, Large B-Cell, Diffuse - mortality ; Male ; Medical research ; Medicine ; Medicine & Public Health ; Medicine, Experimental ; Middle Aged ; Mutation ; Non-Hodgkin's lymphomas ; Oncology ; Phosphoinositide-3 Kinase Inhibitors - therapeutic use ; Phospholipids ; Pyrimidines - adverse effects ; Pyrimidines - therapeutic use ; Quinazolines - adverse effects ; Quinazolines - therapeutic use ; Recurrence ; Relapse ; Safety management ; Subgroups ; Vincristine</subject><ispartof>Leukemia, 2020-08, Vol.34 (8), p.2184-2197</ispartof><rights>The Author(s) 2020. corrected publication 2023</rights><rights>COPYRIGHT 2020 Nature Publishing Group</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2020. corrected publication 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c596t-19fc9ff14661f23c901346a67019014a7364bc5cc5329998204b484e85f1e9ad3</citedby><cites>FETCH-LOGICAL-c596t-19fc9ff14661f23c901346a67019014a7364bc5cc5329998204b484e85f1e9ad3</cites><orcidid>0000-0002-9541-8666</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41375-020-0743-y$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41375-020-0743-y$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32060403$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lenz, Georg</creatorcontrib><creatorcontrib>Hawkes, Eliza</creatorcontrib><creatorcontrib>Verhoef, Gregor</creatorcontrib><creatorcontrib>Haioun, Corinne</creatorcontrib><creatorcontrib>Thye Lim, Soon</creatorcontrib><creatorcontrib>Seog Heo, Dae</creatorcontrib><creatorcontrib>Ardeshna, Kirit</creatorcontrib><creatorcontrib>Chong, Geoffrey</creatorcontrib><creatorcontrib>Haaber, Jacob</creatorcontrib><creatorcontrib>Shi, Wei</creatorcontrib><creatorcontrib>Gorbatchevsky, Igor</creatorcontrib><creatorcontrib>Lippert, Susanne</creatorcontrib><creatorcontrib>Hiemeyer, Florian</creatorcontrib><creatorcontrib>Piraino, Paolo</creatorcontrib><creatorcontrib>Beckmann, Georg</creatorcontrib><creatorcontrib>Peña, Carol</creatorcontrib><creatorcontrib>Buvaylo, Viktoriya</creatorcontrib><creatorcontrib>Childs, Barrett H.</creatorcontrib><creatorcontrib>Salles, Gilles</creatorcontrib><title>Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have adverse outcomes. 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
CD79B
mutational status (NCT02391116). Sixty-seven patients received copanlisib (ABC DLBCL,
n
= 19; GCB DLBCL,
n
= 30; unclassifiable,
n
= 3; missing,
n
= 15). 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
CD79B
mutations (wild type,
n
= 45; mutant,
n
= 9; missing,
n
= 13). 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
BCL2
(53.7%) and
MLL2
(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.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>13</subject><subject>13/51</subject><subject>38</subject><subject>38/23</subject><subject>631/67/1059/602</subject><subject>692/699/67/1990/291/1621/1915</subject><subject>Adult</subject><subject>Adverse events</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>B-cell lymphoma</subject><subject>Biomarkers</subject><subject>Cancer Research</subject><subject>Care and treatment</subject><subject>CD79 Antigens - genetics</subject><subject>Chief operating officers</subject><subject>Critical Care Medicine</subject><subject>Development and progression</subject><subject>Diarrhea</subject><subject>Diseases</subject><subject>Enzyme inhibitors</subject><subject>Female</subject><subject>Hematology</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Hyperglycemia</subject><subject>Hypertension</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Kinases</subject><subject>Lymphocytes B</subject><subject>Lymphoma</subject><subject>Lymphoma, Large B-Cell, Diffuse - drug therapy</subject><subject>Lymphoma, Large B-Cell, Diffuse - genetics</subject><subject>Lymphoma, Large B-Cell, Diffuse - mortality</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Medicine, Experimental</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Non-Hodgkin's lymphomas</subject><subject>Oncology</subject><subject>Phosphoinositide-3 Kinase Inhibitors - therapeutic use</subject><subject>Phospholipids</subject><subject>Pyrimidines - adverse effects</subject><subject>Pyrimidines - therapeutic use</subject><subject>Quinazolines - adverse effects</subject><subject>Quinazolines - therapeutic use</subject><subject>Recurrence</subject><subject>Relapse</subject><subject>Safety 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Georg</creator><creator>Hawkes, Eliza</creator><creator>Verhoef, Gregor</creator><creator>Haioun, Corinne</creator><creator>Thye Lim, Soon</creator><creator>Seog Heo, Dae</creator><creator>Ardeshna, Kirit</creator><creator>Chong, Geoffrey</creator><creator>Haaber, Jacob</creator><creator>Shi, Wei</creator><creator>Gorbatchevsky, Igor</creator><creator>Lippert, Susanne</creator><creator>Hiemeyer, Florian</creator><creator>Piraino, Paolo</creator><creator>Beckmann, Georg</creator><creator>Peña, Carol</creator><creator>Buvaylo, Viktoriya</creator><creator>Childs, Barrett H.</creator><creator>Salles, Gilles</creator><general>Nature Publishing Group UK</general><general>Nature Publishing 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activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma</title><author>Lenz, Georg ; Hawkes, Eliza ; Verhoef, Gregor ; Haioun, Corinne ; Thye Lim, Soon ; Seog Heo, Dae ; Ardeshna, Kirit ; Chong, Geoffrey ; Haaber, Jacob ; Shi, Wei ; Gorbatchevsky, Igor ; Lippert, Susanne ; Hiemeyer, Florian ; Piraino, Paolo ; Beckmann, Georg ; Peña, Carol ; Buvaylo, Viktoriya ; Childs, Barrett H. ; Salles, Gilles</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c596t-19fc9ff14661f23c901346a67019014a7364bc5cc5329998204b484e85f1e9ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>1-Phosphatidylinositol 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and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lenz, Georg</au><au>Hawkes, Eliza</au><au>Verhoef, Gregor</au><au>Haioun, Corinne</au><au>Thye Lim, Soon</au><au>Seog Heo, Dae</au><au>Ardeshna, Kirit</au><au>Chong, Geoffrey</au><au>Haaber, Jacob</au><au>Shi, Wei</au><au>Gorbatchevsky, Igor</au><au>Lippert, Susanne</au><au>Hiemeyer, Florian</au><au>Piraino, Paolo</au><au>Beckmann, Georg</au><au>Peña, Carol</au><au>Buvaylo, Viktoriya</au><au>Childs, Barrett H.</au><au>Salles, Gilles</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2020-08-01</date><risdate>2020</risdate><volume>34</volume><issue>8</issue><spage>2184</spage><epage>2197</epage><pages>2184-2197</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have adverse outcomes. 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
CD79B
mutational status (NCT02391116). Sixty-seven patients received copanlisib (ABC DLBCL,
n
= 19; GCB DLBCL,
n
= 30; unclassifiable,
n
= 3; missing,
n
= 15). 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
CD79B
mutations (wild type,
n
= 45; mutant,
n
= 9; missing,
n
= 13). 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
BCL2
(53.7%) and
MLL2
(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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32060403</pmid><doi>10.1038/s41375-020-0743-y</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-9541-8666</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2020-08, Vol.34 (8), p.2184-2197 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7387311 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | 1-Phosphatidylinositol 3-kinase 13 13/51 38 38/23 631/67/1059/602 692/699/67/1990/291/1621/1915 Adult Adverse events Aged Aged, 80 and over B-cell lymphoma Biomarkers Cancer Research Care and treatment CD79 Antigens - genetics Chief operating officers Critical Care Medicine Development and progression Diarrhea Diseases Enzyme inhibitors Female Hematology High-Throughput Nucleotide Sequencing Humans Hyperglycemia Hypertension Intensive Internal Medicine Kinases Lymphocytes B Lymphoma Lymphoma, Large B-Cell, Diffuse - drug therapy Lymphoma, Large B-Cell, Diffuse - genetics Lymphoma, Large B-Cell, Diffuse - mortality Male Medical research Medicine Medicine & Public Health Medicine, Experimental Middle Aged Mutation Non-Hodgkin's lymphomas Oncology Phosphoinositide-3 Kinase Inhibitors - therapeutic use Phospholipids Pyrimidines - adverse effects Pyrimidines - therapeutic use Quinazolines - adverse effects Quinazolines - therapeutic use Recurrence Relapse Safety management Subgroups Vincristine |
| title | Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma |
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