Outcomes of older patients with NPM1-mutated AML: current treatments and the promise of venetoclax-based regimens
Nucleophosmin-1 mutations (NPM1+) occur in ∼30% of acute myeloid leukemia (AML) patients. Although typically associated with favorable prognosis, the beneficial impact of NPM1+ decreases with increasing age in patients treated with standard intensive chemotherapy (IC) or hypomethylating agents (HMAs...
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creator | Lachowiez, Curtis A. Loghavi, Sanam Kadia, Tapan M. Daver, Naval Borthakur, Gautam Pemmaraju, Naveen Naqvi, Kiran Alvarado, Yesid Yilmaz, Musa Short, Nicholas Ohanian, Maro Pierce, Sherry R. Patel, Keyur P. Qiao, Wei Ning, Jing Sasaki, Koji Takahashi, Koichi Jabbour, Elias Andreeff, Michael Ravandi, Farhad Kantarjian, Hagop M. Konopleva, Marina DiNardo, Courtney D. |
description | Nucleophosmin-1 mutations (NPM1+) occur in ∼30% of acute myeloid leukemia (AML) patients. Although typically associated with favorable prognosis, the beneficial impact of NPM1+ decreases with increasing age in patients treated with standard intensive chemotherapy (IC) or hypomethylating agents (HMAs). This retrospective analysis compared outcomes of NPM1+ AML patients treated with 1 of 3 induction approaches: HMA plus BCL-2 inhibitor venetoclax (VEN), HMA, or IC therapy. Composite complete response (CRc: CR + CR with incomplete count recovery) was seen in 96% (27/28), 36% (17/47), and 89% (204/228) of HMA + VEN, HMA, and IC patients, respectively (HMA + VEN vs HMA, P < .001; HMA + VEN vs IC, P = .10). Older patients (age >65 years) treated with HMA + VEN, HMA, or IC had CR rates of 88%, 28%, and 56%, respectively (HMA + VEN vs HMA, P < .001; HMA + VEN vs IC, P = .01). Significant improvement in overall survival (OS) was seen in patients age >65 years treated with HMA + VEN vs HMA (not reached [NR] vs 0.4 years; P < .001) or IC (NR vs 0.93 years; P = .001). Older patients treated with HMA + VEN had OS of 80% after median 1-year follow-up, with estimated 2-year OS of 70%. In the multivariable Cox model analysis, HMA + VEN was associated with a 69% lower risk of death compared with IC (hazard ratio, 0.31; 95% confidence interval, 0.12-0.83; type I error–adjusted P = .038). HMA + VEN combinations demonstrated impressive results compared with traditional standard-of-care regimens in older patients with NPM1+ AML.
•VEN in combination with HMAs is highly effective for AML with mutant NPM1 (NPM1+).•VEN with HMA therapy could be considered a mutation-targeted treatment in older patients with NPM1+ AML.
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doi_str_mv | 10.1182/bloodadvances.2019001267 |
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•VEN in combination with HMAs is highly effective for AML with mutant NPM1 (NPM1+).•VEN with HMA therapy could be considered a mutation-targeted treatment in older patients with NPM1+ AML.
[Display omitted]</description><identifier>ISSN: 2473-9529</identifier><identifier>EISSN: 2473-9537</identifier><identifier>DOI: 10.1182/bloodadvances.2019001267</identifier><identifier>PMID: 32251497</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Aged ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Bridged Bicyclo Compounds, Heterocyclic ; Humans ; Leukemia, Myeloid, Acute - drug therapy ; Leukemia, Myeloid, Acute - genetics ; Myeloid Neoplasia ; Nuclear Proteins - genetics ; Retrospective Studies ; Sulfonamides</subject><ispartof>Blood advances, 2020-04, Vol.4 (7), p.1311-1320</ispartof><rights>2020 American Society of Hematology</rights><rights>2020 by The American Society of Hematology.</rights><rights>2020 by The American Society of Hematology 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-88371c63a51b9c2ed8b1f7fa3bd83196a22c75bee318c22c2618c60a335d29603</citedby><cites>FETCH-LOGICAL-c479t-88371c63a51b9c2ed8b1f7fa3bd83196a22c75bee318c22c2618c60a335d29603</cites><orcidid>0000-0002-9140-0610 ; 0000-0001-7103-373X ; 0000-0002-1652-7937 ; 0000-0002-9347-2212 ; 0000-0002-1144-1958 ; 0000-0001-5081-2427 ; 0000-0001-8506-0624 ; 0000-0001-8980-3202 ; 0000-0002-1908-3307 ; 0000-0001-9003-0390</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160266/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160266/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32251497$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lachowiez, Curtis A.</creatorcontrib><creatorcontrib>Loghavi, Sanam</creatorcontrib><creatorcontrib>Kadia, Tapan M.</creatorcontrib><creatorcontrib>Daver, Naval</creatorcontrib><creatorcontrib>Borthakur, Gautam</creatorcontrib><creatorcontrib>Pemmaraju, Naveen</creatorcontrib><creatorcontrib>Naqvi, Kiran</creatorcontrib><creatorcontrib>Alvarado, Yesid</creatorcontrib><creatorcontrib>Yilmaz, Musa</creatorcontrib><creatorcontrib>Short, Nicholas</creatorcontrib><creatorcontrib>Ohanian, Maro</creatorcontrib><creatorcontrib>Pierce, Sherry R.</creatorcontrib><creatorcontrib>Patel, Keyur P.</creatorcontrib><creatorcontrib>Qiao, Wei</creatorcontrib><creatorcontrib>Ning, Jing</creatorcontrib><creatorcontrib>Sasaki, Koji</creatorcontrib><creatorcontrib>Takahashi, Koichi</creatorcontrib><creatorcontrib>Jabbour, Elias</creatorcontrib><creatorcontrib>Andreeff, Michael</creatorcontrib><creatorcontrib>Ravandi, Farhad</creatorcontrib><creatorcontrib>Kantarjian, Hagop M.</creatorcontrib><creatorcontrib>Konopleva, Marina</creatorcontrib><creatorcontrib>DiNardo, Courtney D.</creatorcontrib><title>Outcomes of older patients with NPM1-mutated AML: current treatments and the promise of venetoclax-based regimens</title><title>Blood advances</title><addtitle>Blood Adv</addtitle><description>Nucleophosmin-1 mutations (NPM1+) occur in ∼30% of acute myeloid leukemia (AML) patients. Although typically associated with favorable prognosis, the beneficial impact of NPM1+ decreases with increasing age in patients treated with standard intensive chemotherapy (IC) or hypomethylating agents (HMAs). This retrospective analysis compared outcomes of NPM1+ AML patients treated with 1 of 3 induction approaches: HMA plus BCL-2 inhibitor venetoclax (VEN), HMA, or IC therapy. Composite complete response (CRc: CR + CR with incomplete count recovery) was seen in 96% (27/28), 36% (17/47), and 89% (204/228) of HMA + VEN, HMA, and IC patients, respectively (HMA + VEN vs HMA, P < .001; HMA + VEN vs IC, P = .10). Older patients (age >65 years) treated with HMA + VEN, HMA, or IC had CR rates of 88%, 28%, and 56%, respectively (HMA + VEN vs HMA, P < .001; HMA + VEN vs IC, P = .01). Significant improvement in overall survival (OS) was seen in patients age >65 years treated with HMA + VEN vs HMA (not reached [NR] vs 0.4 years; P < .001) or IC (NR vs 0.93 years; P = .001). Older patients treated with HMA + VEN had OS of 80% after median 1-year follow-up, with estimated 2-year OS of 70%. In the multivariable Cox model analysis, HMA + VEN was associated with a 69% lower risk of death compared with IC (hazard ratio, 0.31; 95% confidence interval, 0.12-0.83; type I error–adjusted P = .038). HMA + VEN combinations demonstrated impressive results compared with traditional standard-of-care regimens in older patients with NPM1+ AML.
•VEN in combination with HMAs is highly effective for AML with mutant NPM1 (NPM1+).•VEN with HMA therapy could be considered a mutation-targeted treatment in older patients with NPM1+ AML.
[Display omitted]</description><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Bridged Bicyclo Compounds, Heterocyclic</subject><subject>Humans</subject><subject>Leukemia, Myeloid, Acute - drug therapy</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Myeloid Neoplasia</subject><subject>Nuclear Proteins - genetics</subject><subject>Retrospective Studies</subject><subject>Sulfonamides</subject><issn>2473-9529</issn><issn>2473-9537</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9P3DAQxa0KVBDlKyAfewn1n8SOOVQC1FKkpXCAs-XYE9YoiRfb2bbfHtOFbTlxmpHm996M_RDClBxT2rIv3RCCM25tJgvpmBGqCKFMyA9on9WSV6rhcmfbM7WHDlN6IAWSgjeKfUR7nLGG1kruo8frOdswQsKhx2FwEPHKZA9TTviXz0v88-aKVuOcTQaHT68WJ9jOMZY5zhFMHv-SZnI4LwGvYhh9gmevNUyQgx3M76ozqWgj3PtCp09otzdDgsOXeoDuvn-7Pf9RLa4vLs9PF5WtpcpV23JJreCmoZ2yDFzb0V72hneu5VQJw5iVTQfAaWtLz0SpghjOG8eUIPwAfd34ruZuBGfLodEMehX9aOIfHYzXbyeTX-r7sNaSCsKEKAafXwxieJwhZV3eZmEYzARhTprxVpatdc0L2m5QG0NKEfrtGkr0c2j6TWj6X2hFevT_mVvha0QFONsAUD5r7SHqZEs-FpyPYLN2wb-_5QmL2q_1</recordid><startdate>20200414</startdate><enddate>20200414</enddate><creator>Lachowiez, Curtis A.</creator><creator>Loghavi, Sanam</creator><creator>Kadia, Tapan M.</creator><creator>Daver, Naval</creator><creator>Borthakur, Gautam</creator><creator>Pemmaraju, Naveen</creator><creator>Naqvi, Kiran</creator><creator>Alvarado, Yesid</creator><creator>Yilmaz, Musa</creator><creator>Short, Nicholas</creator><creator>Ohanian, Maro</creator><creator>Pierce, Sherry R.</creator><creator>Patel, Keyur P.</creator><creator>Qiao, Wei</creator><creator>Ning, Jing</creator><creator>Sasaki, Koji</creator><creator>Takahashi, Koichi</creator><creator>Jabbour, Elias</creator><creator>Andreeff, Michael</creator><creator>Ravandi, Farhad</creator><creator>Kantarjian, Hagop M.</creator><creator>Konopleva, Marina</creator><creator>DiNardo, Courtney D.</creator><general>Elsevier Inc</general><general>American Society of Hematology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9140-0610</orcidid><orcidid>https://orcid.org/0000-0001-7103-373X</orcidid><orcidid>https://orcid.org/0000-0002-1652-7937</orcidid><orcidid>https://orcid.org/0000-0002-9347-2212</orcidid><orcidid>https://orcid.org/0000-0002-1144-1958</orcidid><orcidid>https://orcid.org/0000-0001-5081-2427</orcidid><orcidid>https://orcid.org/0000-0001-8506-0624</orcidid><orcidid>https://orcid.org/0000-0001-8980-3202</orcidid><orcidid>https://orcid.org/0000-0002-1908-3307</orcidid><orcidid>https://orcid.org/0000-0001-9003-0390</orcidid></search><sort><creationdate>20200414</creationdate><title>Outcomes of older patients with NPM1-mutated AML: current treatments and the promise of venetoclax-based regimens</title><author>Lachowiez, Curtis A. ; Loghavi, Sanam ; Kadia, Tapan M. ; Daver, Naval ; Borthakur, Gautam ; Pemmaraju, Naveen ; Naqvi, Kiran ; Alvarado, Yesid ; Yilmaz, Musa ; Short, Nicholas ; Ohanian, Maro ; Pierce, Sherry R. ; Patel, Keyur P. ; Qiao, Wei ; Ning, Jing ; Sasaki, Koji ; Takahashi, Koichi ; Jabbour, Elias ; Andreeff, Michael ; Ravandi, Farhad ; Kantarjian, Hagop M. ; Konopleva, Marina ; DiNardo, Courtney D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-88371c63a51b9c2ed8b1f7fa3bd83196a22c75bee318c22c2618c60a335d29603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aged</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Bridged Bicyclo Compounds, Heterocyclic</topic><topic>Humans</topic><topic>Leukemia, Myeloid, Acute - drug therapy</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Myeloid Neoplasia</topic><topic>Nuclear Proteins - genetics</topic><topic>Retrospective Studies</topic><topic>Sulfonamides</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lachowiez, Curtis A.</creatorcontrib><creatorcontrib>Loghavi, Sanam</creatorcontrib><creatorcontrib>Kadia, Tapan M.</creatorcontrib><creatorcontrib>Daver, Naval</creatorcontrib><creatorcontrib>Borthakur, Gautam</creatorcontrib><creatorcontrib>Pemmaraju, Naveen</creatorcontrib><creatorcontrib>Naqvi, Kiran</creatorcontrib><creatorcontrib>Alvarado, Yesid</creatorcontrib><creatorcontrib>Yilmaz, Musa</creatorcontrib><creatorcontrib>Short, Nicholas</creatorcontrib><creatorcontrib>Ohanian, Maro</creatorcontrib><creatorcontrib>Pierce, Sherry R.</creatorcontrib><creatorcontrib>Patel, Keyur P.</creatorcontrib><creatorcontrib>Qiao, Wei</creatorcontrib><creatorcontrib>Ning, Jing</creatorcontrib><creatorcontrib>Sasaki, Koji</creatorcontrib><creatorcontrib>Takahashi, Koichi</creatorcontrib><creatorcontrib>Jabbour, Elias</creatorcontrib><creatorcontrib>Andreeff, Michael</creatorcontrib><creatorcontrib>Ravandi, Farhad</creatorcontrib><creatorcontrib>Kantarjian, Hagop M.</creatorcontrib><creatorcontrib>Konopleva, Marina</creatorcontrib><creatorcontrib>DiNardo, Courtney D.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Blood advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lachowiez, Curtis A.</au><au>Loghavi, Sanam</au><au>Kadia, Tapan M.</au><au>Daver, Naval</au><au>Borthakur, Gautam</au><au>Pemmaraju, Naveen</au><au>Naqvi, Kiran</au><au>Alvarado, Yesid</au><au>Yilmaz, Musa</au><au>Short, Nicholas</au><au>Ohanian, Maro</au><au>Pierce, Sherry R.</au><au>Patel, Keyur P.</au><au>Qiao, Wei</au><au>Ning, Jing</au><au>Sasaki, Koji</au><au>Takahashi, Koichi</au><au>Jabbour, Elias</au><au>Andreeff, Michael</au><au>Ravandi, Farhad</au><au>Kantarjian, Hagop M.</au><au>Konopleva, Marina</au><au>DiNardo, Courtney D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Outcomes of older patients with NPM1-mutated AML: current treatments and the promise of venetoclax-based regimens</atitle><jtitle>Blood advances</jtitle><addtitle>Blood Adv</addtitle><date>2020-04-14</date><risdate>2020</risdate><volume>4</volume><issue>7</issue><spage>1311</spage><epage>1320</epage><pages>1311-1320</pages><issn>2473-9529</issn><eissn>2473-9537</eissn><abstract>Nucleophosmin-1 mutations (NPM1+) occur in ∼30% of acute myeloid leukemia (AML) patients. Although typically associated with favorable prognosis, the beneficial impact of NPM1+ decreases with increasing age in patients treated with standard intensive chemotherapy (IC) or hypomethylating agents (HMAs). This retrospective analysis compared outcomes of NPM1+ AML patients treated with 1 of 3 induction approaches: HMA plus BCL-2 inhibitor venetoclax (VEN), HMA, or IC therapy. Composite complete response (CRc: CR + CR with incomplete count recovery) was seen in 96% (27/28), 36% (17/47), and 89% (204/228) of HMA + VEN, HMA, and IC patients, respectively (HMA + VEN vs HMA, P < .001; HMA + VEN vs IC, P = .10). Older patients (age >65 years) treated with HMA + VEN, HMA, or IC had CR rates of 88%, 28%, and 56%, respectively (HMA + VEN vs HMA, P < .001; HMA + VEN vs IC, P = .01). Significant improvement in overall survival (OS) was seen in patients age >65 years treated with HMA + VEN vs HMA (not reached [NR] vs 0.4 years; P < .001) or IC (NR vs 0.93 years; P = .001). Older patients treated with HMA + VEN had OS of 80% after median 1-year follow-up, with estimated 2-year OS of 70%. In the multivariable Cox model analysis, HMA + VEN was associated with a 69% lower risk of death compared with IC (hazard ratio, 0.31; 95% confidence interval, 0.12-0.83; type I error–adjusted P = .038). HMA + VEN combinations demonstrated impressive results compared with traditional standard-of-care regimens in older patients with NPM1+ AML.
•VEN in combination with HMAs is highly effective for AML with mutant NPM1 (NPM1+).•VEN with HMA therapy could be considered a mutation-targeted treatment in older patients with NPM1+ AML.
[Display omitted]</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32251497</pmid><doi>10.1182/bloodadvances.2019001267</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-9140-0610</orcidid><orcidid>https://orcid.org/0000-0001-7103-373X</orcidid><orcidid>https://orcid.org/0000-0002-1652-7937</orcidid><orcidid>https://orcid.org/0000-0002-9347-2212</orcidid><orcidid>https://orcid.org/0000-0002-1144-1958</orcidid><orcidid>https://orcid.org/0000-0001-5081-2427</orcidid><orcidid>https://orcid.org/0000-0001-8506-0624</orcidid><orcidid>https://orcid.org/0000-0001-8980-3202</orcidid><orcidid>https://orcid.org/0000-0002-1908-3307</orcidid><orcidid>https://orcid.org/0000-0001-9003-0390</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Aged Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bridged Bicyclo Compounds, Heterocyclic Humans Leukemia, Myeloid, Acute - drug therapy Leukemia, Myeloid, Acute - genetics Myeloid Neoplasia Nuclear Proteins - genetics Retrospective Studies Sulfonamides |
title | Outcomes of older patients with NPM1-mutated AML: current treatments and the promise of venetoclax-based regimens |
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