C‐MYC–positive relapsed and refractory, diffuse large B‐cell lymphoma: Impact of additional “hits” and outcomes with subsequent therapy
BACKGROUND The impact of MYC proto‐oncogene, basic helix‐loop‐helix (MYC) translocations (with or without additional rearrangements involving the B‐cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B‐cell lymphoma (DLBCL) who experie...
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| Veröffentlicht in: | Cancer 2017-11, Vol.123 (22), p.4411-4418 |
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| container_title | Cancer |
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| creator | Epperla, Narendranath Maddocks, Kami J. Salhab, Mohammed Chavez, Julio C. Reddy, Nishitha Karmali, Reem Umyarova, Elvira Bachanova, Veronika Costa, Cristiana Glenn, Martha Calzada, Oscar Xavier, Ana C. Zhou, Zheng Hossain, Nasheed M. Hernandez‐Ilizaliturri, Francisco J. Al‐Mansour, Zeina Barta, Stefan K. Chhabra, Saurabh Lansigan, Frederick Mehta, Amitkumar Jaglal, Michael V. Evans, Andrew Flowers, Christopher R. Cohen, Jonathon B. Fenske, Timothy S. Hamadani, Mehdi Costa, Luciano J. |
| description | BACKGROUND
The impact of MYC proto‐oncogene, basic helix‐loop‐helix (MYC) translocations (with or without additional rearrangements involving the B‐cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B‐cell lymphoma (DLBCL) who experience primary treatment failure is not well defined.
METHODS
This was a multicenter, retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in patients with DLBCL who failed to achieve complete remission or relapsed within 6 months after they completed upfront chemoimmunotherapy.
RESULTS
The authors examined response to salvage therapy, receipt of hematopoietic cell transplantation (HCT), and survival outcomes in MYC‐negative (n = 120), MYC‐positive single hit (SH) (n = 20), and MYC‐positive double hit/triple hit (DH/TH) (n = 35) cohorts. The overall response rate in these cohorts to first salvage therapy (51%, 50%, and 54%, respectively) and receipt of HCT (52%, 40%, and 43%, respectively) were comparable between the 3 cohorts. The 2‐year overall survival rate was 29.9% in the MYC‐negative cohort, 0% in the MYC‐positive SH cohort, and 9.9% in the MYC‐positive DH/TH cohort (P < .001), and no difference was observed between the SH and DH/TH cohorts (P = .8). The higher risk of death for patients with MYC‐positive SH DLBCL (hazard ratio, 1.70; 95% confidence interval, 0.98‐2.96; P = .06) and those with MYC‐positive DH/TH DLBCL (hazard ratio, 2.22; 95% confidence interval, 1.41‐3.50; P = .001) persisted after adjusting for covariates. For patients who underwent autologous HCT, the 2‐year overall survival rate was 55.4% in the MYC‐negative cohort, 0% in the MYC‐positive SH cohort, and 19.4% in the MYC‐positive DH/TH cohort (P < .001). All 4 MYC‐positive patients who underwent allogeneic HCT relapsed in |
| doi_str_mv | 10.1002/cncr.30895 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1924595579</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1924595579</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3935-3fe3e9916d68eb97cf5f3d52563ab912c0683e5765bd51692992886fbef46c203</originalsourceid><addsrcrecordid>eNp9kc2K1TAUx4MoznV04wNIwI2IHfPRtIk7LX4MjAqioKuSJifeDm1Tk9ahu_sIilt9ufskpnNHFy7c5HDgd37knD9Cdyk5oYSwx2Yw4YQTqcQ1tKFElRmhObuONoQQmYmcfzxCt2I8T23JBL-JjpgscyVyuUHfq_3u2-tP6f0x-thO7VfAATo9RrBYDzY1Lmgz-bA8wrZ1bo6AOx0-A36WJg10He6Wftz6Xj_Bp_2YWOwd1tYmmR90h_e7n9t2ivvdr0uhnyfje4j4op22OM5NhC8zDBOethD0uNxGN5zuIty5qsfow4vn76tX2dnbl6fV07PMcMVFxh1wUIoWtpDQqNI44bgVTBRcN4oyQwrJQZSFaKyghWJKMSkL14DLC8MIP0YPDt4x-PSBONV9G9d99AB-jjVVLBdKiFIl9P4_6LmfQ9ptpYRilAq5Ug8PlAk-xnS3egxtr8NSU1KvQdVrUPVlUAm-d6Wcmx7sX_RPMgmgB-Ci7WD5j6qu3lTvDtLfzlmj1A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1959211589</pqid></control><display><type>article</type><title>C‐MYC–positive relapsed and refractory, diffuse large B‐cell lymphoma: Impact of additional “hits” and outcomes with subsequent therapy</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Wiley Free Content</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Epperla, Narendranath ; Maddocks, Kami J. ; Salhab, Mohammed ; Chavez, Julio C. ; Reddy, Nishitha ; Karmali, Reem ; Umyarova, Elvira ; Bachanova, Veronika ; Costa, Cristiana ; Glenn, Martha ; Calzada, Oscar ; Xavier, Ana C. ; Zhou, Zheng ; Hossain, Nasheed M. ; Hernandez‐Ilizaliturri, Francisco J. ; Al‐Mansour, Zeina ; Barta, Stefan K. ; Chhabra, Saurabh ; Lansigan, Frederick ; Mehta, Amitkumar ; Jaglal, Michael V. ; Evans, Andrew ; Flowers, Christopher R. ; Cohen, Jonathon B. ; Fenske, Timothy S. ; Hamadani, Mehdi ; Costa, Luciano J.</creator><creatorcontrib>Epperla, Narendranath ; Maddocks, Kami J. ; Salhab, Mohammed ; Chavez, Julio C. ; Reddy, Nishitha ; Karmali, Reem ; Umyarova, Elvira ; Bachanova, Veronika ; Costa, Cristiana ; Glenn, Martha ; Calzada, Oscar ; Xavier, Ana C. ; Zhou, Zheng ; Hossain, Nasheed M. ; Hernandez‐Ilizaliturri, Francisco J. ; Al‐Mansour, Zeina ; Barta, Stefan K. ; Chhabra, Saurabh ; Lansigan, Frederick ; Mehta, Amitkumar ; Jaglal, Michael V. ; Evans, Andrew ; Flowers, Christopher R. ; Cohen, Jonathon B. ; Fenske, Timothy S. ; Hamadani, Mehdi ; Costa, Luciano J.</creatorcontrib><description>BACKGROUND
The impact of MYC proto‐oncogene, basic helix‐loop‐helix (MYC) translocations (with or without additional rearrangements involving the B‐cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B‐cell lymphoma (DLBCL) who experience primary treatment failure is not well defined.
METHODS
This was a multicenter, retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in patients with DLBCL who failed to achieve complete remission or relapsed within 6 months after they completed upfront chemoimmunotherapy.
RESULTS
The authors examined response to salvage therapy, receipt of hematopoietic cell transplantation (HCT), and survival outcomes in MYC‐negative (n = 120), MYC‐positive single hit (SH) (n = 20), and MYC‐positive double hit/triple hit (DH/TH) (n = 35) cohorts. The overall response rate in these cohorts to first salvage therapy (51%, 50%, and 54%, respectively) and receipt of HCT (52%, 40%, and 43%, respectively) were comparable between the 3 cohorts. The 2‐year overall survival rate was 29.9% in the MYC‐negative cohort, 0% in the MYC‐positive SH cohort, and 9.9% in the MYC‐positive DH/TH cohort (P < .001), and no difference was observed between the SH and DH/TH cohorts (P = .8). The higher risk of death for patients with MYC‐positive SH DLBCL (hazard ratio, 1.70; 95% confidence interval, 0.98‐2.96; P = .06) and those with MYC‐positive DH/TH DLBCL (hazard ratio, 2.22; 95% confidence interval, 1.41‐3.50; P = .001) persisted after adjusting for covariates. For patients who underwent autologous HCT, the 2‐year overall survival rate was 55.4% in the MYC‐negative cohort, 0% in the MYC‐positive SH cohort, and 19.4% in the MYC‐positive DH/TH cohort (P < .001). All 4 MYC‐positive patients who underwent allogeneic HCT relapsed in <4 months.
CONCLUSIONS
Patients with MYC‐positive DLBCL who experience primary treatment failure have response rates to similar to those achieved by salvage therapy compared with their MYC‐negative counterparts, but their survival is dismal irrespective of additional “hits” and HCT, representing an unmet medical need. Cancer 2017;123:4411‐8. © 2017 American Cancer Society.
The impact of MYC translocations (with or without additional BCL2 or BCL6 gene rearrangements) on response to salvage therapy and survival in patients with diffuse large B‐cell lymphoma who experience primary treatment failure is not well defined. In this retrospective study, patients with MYC‐positive DLBCL who fail on primary treatment have response rates similar to those observed after salvage therapy compared with their MYC‐negative counterparts, but their survival is dismal irrespective of additional “hits” and hematopoietic cell transplantation, representing an unmet medical need.</description><identifier>ISSN: 0008-543X</identifier><identifier>EISSN: 1097-0142</identifier><identifier>DOI: 10.1002/cncr.30895</identifier><identifier>PMID: 28749548</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Autografts ; B-cell lymphoma ; basic helix‐loop‐helix (MYC) ; Bcl-6 protein ; c-Myc protein ; Cancer ; Cell survival ; Confidence intervals ; diffuse large B‐cell lymphoma (DLBCL) ; Drug Resistance, Neoplasm - genetics ; Female ; Genes, myc ; Health risk assessment ; Helix-loop-helix proteins (basic) ; hematopoietic cell transplantation (HCT) ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphocytes B ; Lymphoma ; Lymphoma, Large B-Cell, Diffuse - genetics ; Lymphoma, Large B-Cell, Diffuse - mortality ; Lymphoma, Large B-Cell, Diffuse - pathology ; Lymphoma, Large B-Cell, Diffuse - therapy ; Male ; Middle Aged ; Myc protein ; MYC proto‐oncogene ; non‐Hodgkin lymphoma ; Oncology ; Patients ; Recurrence ; Remission ; Retrospective Studies ; Salvage ; Salvage Therapy ; Survival ; Therapy ; Translocation ; Translocation, Genetic ; Transplantation ; Treatment Outcome ; Young Adult</subject><ispartof>Cancer, 2017-11, Vol.123 (22), p.4411-4418</ispartof><rights>2017 American Cancer Society</rights><rights>2017 American Cancer Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3935-3fe3e9916d68eb97cf5f3d52563ab912c0683e5765bd51692992886fbef46c203</citedby><cites>FETCH-LOGICAL-c3935-3fe3e9916d68eb97cf5f3d52563ab912c0683e5765bd51692992886fbef46c203</cites><orcidid>0000-0002-9524-3990 ; 0000-0002-8216-3457 ; 0000-0002-9325-432X ; 0000-0002-3659-3798</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcncr.30895$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcncr.30895$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28749548$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Epperla, Narendranath</creatorcontrib><creatorcontrib>Maddocks, Kami J.</creatorcontrib><creatorcontrib>Salhab, Mohammed</creatorcontrib><creatorcontrib>Chavez, Julio C.</creatorcontrib><creatorcontrib>Reddy, Nishitha</creatorcontrib><creatorcontrib>Karmali, Reem</creatorcontrib><creatorcontrib>Umyarova, Elvira</creatorcontrib><creatorcontrib>Bachanova, Veronika</creatorcontrib><creatorcontrib>Costa, Cristiana</creatorcontrib><creatorcontrib>Glenn, Martha</creatorcontrib><creatorcontrib>Calzada, Oscar</creatorcontrib><creatorcontrib>Xavier, Ana C.</creatorcontrib><creatorcontrib>Zhou, Zheng</creatorcontrib><creatorcontrib>Hossain, Nasheed M.</creatorcontrib><creatorcontrib>Hernandez‐Ilizaliturri, Francisco J.</creatorcontrib><creatorcontrib>Al‐Mansour, Zeina</creatorcontrib><creatorcontrib>Barta, Stefan K.</creatorcontrib><creatorcontrib>Chhabra, Saurabh</creatorcontrib><creatorcontrib>Lansigan, Frederick</creatorcontrib><creatorcontrib>Mehta, Amitkumar</creatorcontrib><creatorcontrib>Jaglal, Michael V.</creatorcontrib><creatorcontrib>Evans, Andrew</creatorcontrib><creatorcontrib>Flowers, Christopher R.</creatorcontrib><creatorcontrib>Cohen, Jonathon B.</creatorcontrib><creatorcontrib>Fenske, Timothy S.</creatorcontrib><creatorcontrib>Hamadani, Mehdi</creatorcontrib><creatorcontrib>Costa, Luciano J.</creatorcontrib><title>C‐MYC–positive relapsed and refractory, diffuse large B‐cell lymphoma: Impact of additional “hits” and outcomes with subsequent therapy</title><title>Cancer</title><addtitle>Cancer</addtitle><description>BACKGROUND
The impact of MYC proto‐oncogene, basic helix‐loop‐helix (MYC) translocations (with or without additional rearrangements involving the B‐cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B‐cell lymphoma (DLBCL) who experience primary treatment failure is not well defined.
METHODS
This was a multicenter, retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in patients with DLBCL who failed to achieve complete remission or relapsed within 6 months after they completed upfront chemoimmunotherapy.
RESULTS
The authors examined response to salvage therapy, receipt of hematopoietic cell transplantation (HCT), and survival outcomes in MYC‐negative (n = 120), MYC‐positive single hit (SH) (n = 20), and MYC‐positive double hit/triple hit (DH/TH) (n = 35) cohorts. The overall response rate in these cohorts to first salvage therapy (51%, 50%, and 54%, respectively) and receipt of HCT (52%, 40%, and 43%, respectively) were comparable between the 3 cohorts. The 2‐year overall survival rate was 29.9% in the MYC‐negative cohort, 0% in the MYC‐positive SH cohort, and 9.9% in the MYC‐positive DH/TH cohort (P < .001), and no difference was observed between the SH and DH/TH cohorts (P = .8). The higher risk of death for patients with MYC‐positive SH DLBCL (hazard ratio, 1.70; 95% confidence interval, 0.98‐2.96; P = .06) and those with MYC‐positive DH/TH DLBCL (hazard ratio, 2.22; 95% confidence interval, 1.41‐3.50; P = .001) persisted after adjusting for covariates. For patients who underwent autologous HCT, the 2‐year overall survival rate was 55.4% in the MYC‐negative cohort, 0% in the MYC‐positive SH cohort, and 19.4% in the MYC‐positive DH/TH cohort (P < .001). All 4 MYC‐positive patients who underwent allogeneic HCT relapsed in <4 months.
CONCLUSIONS
Patients with MYC‐positive DLBCL who experience primary treatment failure have response rates to similar to those achieved by salvage therapy compared with their MYC‐negative counterparts, but their survival is dismal irrespective of additional “hits” and HCT, representing an unmet medical need. Cancer 2017;123:4411‐8. © 2017 American Cancer Society.
The impact of MYC translocations (with or without additional BCL2 or BCL6 gene rearrangements) on response to salvage therapy and survival in patients with diffuse large B‐cell lymphoma who experience primary treatment failure is not well defined. In this retrospective study, patients with MYC‐positive DLBCL who fail on primary treatment have response rates similar to those observed after salvage therapy compared with their MYC‐negative counterparts, but their survival is dismal irrespective of additional “hits” and hematopoietic cell transplantation, representing an unmet medical need.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Autografts</subject><subject>B-cell lymphoma</subject><subject>basic helix‐loop‐helix (MYC)</subject><subject>Bcl-6 protein</subject><subject>c-Myc protein</subject><subject>Cancer</subject><subject>Cell survival</subject><subject>Confidence intervals</subject><subject>diffuse large B‐cell lymphoma (DLBCL)</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Female</subject><subject>Genes, myc</subject><subject>Health risk assessment</subject><subject>Helix-loop-helix proteins (basic)</subject><subject>hematopoietic cell transplantation (HCT)</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Humans</subject><subject>Lymphocytes B</subject><subject>Lymphoma</subject><subject>Lymphoma, Large B-Cell, Diffuse - genetics</subject><subject>Lymphoma, Large B-Cell, Diffuse - mortality</subject><subject>Lymphoma, Large B-Cell, Diffuse - pathology</subject><subject>Lymphoma, Large B-Cell, Diffuse - therapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myc protein</subject><subject>MYC proto‐oncogene</subject><subject>non‐Hodgkin lymphoma</subject><subject>Oncology</subject><subject>Patients</subject><subject>Recurrence</subject><subject>Remission</subject><subject>Retrospective Studies</subject><subject>Salvage</subject><subject>Salvage Therapy</subject><subject>Survival</subject><subject>Therapy</subject><subject>Translocation</subject><subject>Translocation, Genetic</subject><subject>Transplantation</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>0008-543X</issn><issn>1097-0142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2K1TAUx4MoznV04wNIwI2IHfPRtIk7LX4MjAqioKuSJifeDm1Tk9ahu_sIilt9ufskpnNHFy7c5HDgd37knD9Cdyk5oYSwx2Yw4YQTqcQ1tKFElRmhObuONoQQmYmcfzxCt2I8T23JBL-JjpgscyVyuUHfq_3u2-tP6f0x-thO7VfAATo9RrBYDzY1Lmgz-bA8wrZ1bo6AOx0-A36WJg10He6Wftz6Xj_Bp_2YWOwd1tYmmR90h_e7n9t2ivvdr0uhnyfje4j4op22OM5NhC8zDBOethD0uNxGN5zuIty5qsfow4vn76tX2dnbl6fV07PMcMVFxh1wUIoWtpDQqNI44bgVTBRcN4oyQwrJQZSFaKyghWJKMSkL14DLC8MIP0YPDt4x-PSBONV9G9d99AB-jjVVLBdKiFIl9P4_6LmfQ9ptpYRilAq5Ug8PlAk-xnS3egxtr8NSU1KvQdVrUPVlUAm-d6Wcmx7sX_RPMgmgB-Ci7WD5j6qu3lTvDtLfzlmj1A</recordid><startdate>20171115</startdate><enddate>20171115</enddate><creator>Epperla, Narendranath</creator><creator>Maddocks, Kami J.</creator><creator>Salhab, Mohammed</creator><creator>Chavez, Julio C.</creator><creator>Reddy, Nishitha</creator><creator>Karmali, Reem</creator><creator>Umyarova, Elvira</creator><creator>Bachanova, Veronika</creator><creator>Costa, Cristiana</creator><creator>Glenn, Martha</creator><creator>Calzada, Oscar</creator><creator>Xavier, Ana C.</creator><creator>Zhou, Zheng</creator><creator>Hossain, Nasheed M.</creator><creator>Hernandez‐Ilizaliturri, Francisco J.</creator><creator>Al‐Mansour, Zeina</creator><creator>Barta, Stefan K.</creator><creator>Chhabra, Saurabh</creator><creator>Lansigan, Frederick</creator><creator>Mehta, Amitkumar</creator><creator>Jaglal, Michael V.</creator><creator>Evans, Andrew</creator><creator>Flowers, Christopher R.</creator><creator>Cohen, Jonathon B.</creator><creator>Fenske, Timothy S.</creator><creator>Hamadani, Mehdi</creator><creator>Costa, Luciano J.</creator><general>Wiley Subscription Services, Inc</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>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9524-3990</orcidid><orcidid>https://orcid.org/0000-0002-8216-3457</orcidid><orcidid>https://orcid.org/0000-0002-9325-432X</orcidid><orcidid>https://orcid.org/0000-0002-3659-3798</orcidid></search><sort><creationdate>20171115</creationdate><title>C‐MYC–positive relapsed and refractory, diffuse large B‐cell lymphoma: Impact of additional “hits” and outcomes with subsequent therapy</title><author>Epperla, Narendranath ; Maddocks, Kami J. ; Salhab, Mohammed ; Chavez, Julio C. ; Reddy, Nishitha ; Karmali, Reem ; Umyarova, Elvira ; Bachanova, Veronika ; Costa, Cristiana ; Glenn, Martha ; Calzada, Oscar ; Xavier, Ana C. ; Zhou, Zheng ; Hossain, Nasheed M. ; Hernandez‐Ilizaliturri, Francisco J. ; Al‐Mansour, Zeina ; Barta, Stefan K. ; Chhabra, Saurabh ; Lansigan, Frederick ; Mehta, Amitkumar ; Jaglal, Michael V. ; Evans, Andrew ; Flowers, Christopher R. ; Cohen, Jonathon B. ; Fenske, Timothy S. ; Hamadani, Mehdi ; Costa, Luciano J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3935-3fe3e9916d68eb97cf5f3d52563ab912c0683e5765bd51692992886fbef46c203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Autografts</topic><topic>B-cell lymphoma</topic><topic>basic helix‐loop‐helix (MYC)</topic><topic>Bcl-6 protein</topic><topic>c-Myc protein</topic><topic>Cancer</topic><topic>Cell survival</topic><topic>Confidence intervals</topic><topic>diffuse large B‐cell lymphoma (DLBCL)</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Female</topic><topic>Genes, myc</topic><topic>Health risk assessment</topic><topic>Helix-loop-helix proteins (basic)</topic><topic>hematopoietic cell transplantation (HCT)</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Humans</topic><topic>Lymphocytes B</topic><topic>Lymphoma</topic><topic>Lymphoma, Large B-Cell, Diffuse - genetics</topic><topic>Lymphoma, Large B-Cell, Diffuse - mortality</topic><topic>Lymphoma, Large B-Cell, Diffuse - pathology</topic><topic>Lymphoma, Large B-Cell, Diffuse - therapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myc protein</topic><topic>MYC proto‐oncogene</topic><topic>non‐Hodgkin lymphoma</topic><topic>Oncology</topic><topic>Patients</topic><topic>Recurrence</topic><topic>Remission</topic><topic>Retrospective Studies</topic><topic>Salvage</topic><topic>Salvage Therapy</topic><topic>Survival</topic><topic>Therapy</topic><topic>Translocation</topic><topic>Translocation, Genetic</topic><topic>Transplantation</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Epperla, Narendranath</creatorcontrib><creatorcontrib>Maddocks, Kami J.</creatorcontrib><creatorcontrib>Salhab, Mohammed</creatorcontrib><creatorcontrib>Chavez, Julio C.</creatorcontrib><creatorcontrib>Reddy, Nishitha</creatorcontrib><creatorcontrib>Karmali, Reem</creatorcontrib><creatorcontrib>Umyarova, Elvira</creatorcontrib><creatorcontrib>Bachanova, Veronika</creatorcontrib><creatorcontrib>Costa, Cristiana</creatorcontrib><creatorcontrib>Glenn, Martha</creatorcontrib><creatorcontrib>Calzada, Oscar</creatorcontrib><creatorcontrib>Xavier, Ana C.</creatorcontrib><creatorcontrib>Zhou, Zheng</creatorcontrib><creatorcontrib>Hossain, Nasheed M.</creatorcontrib><creatorcontrib>Hernandez‐Ilizaliturri, Francisco J.</creatorcontrib><creatorcontrib>Al‐Mansour, Zeina</creatorcontrib><creatorcontrib>Barta, Stefan K.</creatorcontrib><creatorcontrib>Chhabra, Saurabh</creatorcontrib><creatorcontrib>Lansigan, Frederick</creatorcontrib><creatorcontrib>Mehta, Amitkumar</creatorcontrib><creatorcontrib>Jaglal, Michael V.</creatorcontrib><creatorcontrib>Evans, Andrew</creatorcontrib><creatorcontrib>Flowers, Christopher R.</creatorcontrib><creatorcontrib>Cohen, Jonathon B.</creatorcontrib><creatorcontrib>Fenske, Timothy S.</creatorcontrib><creatorcontrib>Hamadani, Mehdi</creatorcontrib><creatorcontrib>Costa, Luciano J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Epperla, Narendranath</au><au>Maddocks, Kami J.</au><au>Salhab, Mohammed</au><au>Chavez, Julio C.</au><au>Reddy, Nishitha</au><au>Karmali, Reem</au><au>Umyarova, Elvira</au><au>Bachanova, Veronika</au><au>Costa, Cristiana</au><au>Glenn, Martha</au><au>Calzada, Oscar</au><au>Xavier, Ana C.</au><au>Zhou, Zheng</au><au>Hossain, Nasheed M.</au><au>Hernandez‐Ilizaliturri, Francisco J.</au><au>Al‐Mansour, Zeina</au><au>Barta, Stefan K.</au><au>Chhabra, Saurabh</au><au>Lansigan, Frederick</au><au>Mehta, Amitkumar</au><au>Jaglal, Michael V.</au><au>Evans, Andrew</au><au>Flowers, Christopher R.</au><au>Cohen, Jonathon B.</au><au>Fenske, Timothy S.</au><au>Hamadani, Mehdi</au><au>Costa, Luciano J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>C‐MYC–positive relapsed and refractory, diffuse large B‐cell lymphoma: Impact of additional “hits” and outcomes with subsequent therapy</atitle><jtitle>Cancer</jtitle><addtitle>Cancer</addtitle><date>2017-11-15</date><risdate>2017</risdate><volume>123</volume><issue>22</issue><spage>4411</spage><epage>4418</epage><pages>4411-4418</pages><issn>0008-543X</issn><eissn>1097-0142</eissn><abstract>BACKGROUND
The impact of MYC proto‐oncogene, basic helix‐loop‐helix (MYC) translocations (with or without additional rearrangements involving the B‐cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B‐cell lymphoma (DLBCL) who experience primary treatment failure is not well defined.
METHODS
This was a multicenter, retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in patients with DLBCL who failed to achieve complete remission or relapsed within 6 months after they completed upfront chemoimmunotherapy.
RESULTS
The authors examined response to salvage therapy, receipt of hematopoietic cell transplantation (HCT), and survival outcomes in MYC‐negative (n = 120), MYC‐positive single hit (SH) (n = 20), and MYC‐positive double hit/triple hit (DH/TH) (n = 35) cohorts. The overall response rate in these cohorts to first salvage therapy (51%, 50%, and 54%, respectively) and receipt of HCT (52%, 40%, and 43%, respectively) were comparable between the 3 cohorts. The 2‐year overall survival rate was 29.9% in the MYC‐negative cohort, 0% in the MYC‐positive SH cohort, and 9.9% in the MYC‐positive DH/TH cohort (P < .001), and no difference was observed between the SH and DH/TH cohorts (P = .8). The higher risk of death for patients with MYC‐positive SH DLBCL (hazard ratio, 1.70; 95% confidence interval, 0.98‐2.96; P = .06) and those with MYC‐positive DH/TH DLBCL (hazard ratio, 2.22; 95% confidence interval, 1.41‐3.50; P = .001) persisted after adjusting for covariates. For patients who underwent autologous HCT, the 2‐year overall survival rate was 55.4% in the MYC‐negative cohort, 0% in the MYC‐positive SH cohort, and 19.4% in the MYC‐positive DH/TH cohort (P < .001). All 4 MYC‐positive patients who underwent allogeneic HCT relapsed in <4 months.
CONCLUSIONS
Patients with MYC‐positive DLBCL who experience primary treatment failure have response rates to similar to those achieved by salvage therapy compared with their MYC‐negative counterparts, but their survival is dismal irrespective of additional “hits” and HCT, representing an unmet medical need. Cancer 2017;123:4411‐8. © 2017 American Cancer Society.
The impact of MYC translocations (with or without additional BCL2 or BCL6 gene rearrangements) on response to salvage therapy and survival in patients with diffuse large B‐cell lymphoma who experience primary treatment failure is not well defined. In this retrospective study, patients with MYC‐positive DLBCL who fail on primary treatment have response rates similar to those observed after salvage therapy compared with their MYC‐negative counterparts, but their survival is dismal irrespective of additional “hits” and hematopoietic cell transplantation, representing an unmet medical need.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28749548</pmid><doi>10.1002/cncr.30895</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-9524-3990</orcidid><orcidid>https://orcid.org/0000-0002-8216-3457</orcidid><orcidid>https://orcid.org/0000-0002-9325-432X</orcidid><orcidid>https://orcid.org/0000-0002-3659-3798</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer, 2017-11, Vol.123 (22), p.4411-4418 |
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| language | eng |
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| subjects | Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols - therapeutic use Autografts B-cell lymphoma basic helix‐loop‐helix (MYC) Bcl-6 protein c-Myc protein Cancer Cell survival Confidence intervals diffuse large B‐cell lymphoma (DLBCL) Drug Resistance, Neoplasm - genetics Female Genes, myc Health risk assessment Helix-loop-helix proteins (basic) hematopoietic cell transplantation (HCT) Hematopoietic Stem Cell Transplantation Humans Lymphocytes B Lymphoma Lymphoma, Large B-Cell, Diffuse - genetics Lymphoma, Large B-Cell, Diffuse - mortality Lymphoma, Large B-Cell, Diffuse - pathology Lymphoma, Large B-Cell, Diffuse - therapy Male Middle Aged Myc protein MYC proto‐oncogene non‐Hodgkin lymphoma Oncology Patients Recurrence Remission Retrospective Studies Salvage Salvage Therapy Survival Therapy Translocation Translocation, Genetic Transplantation Treatment Outcome Young Adult |
| title | C‐MYC–positive relapsed and refractory, diffuse large B‐cell lymphoma: Impact of additional “hits” and outcomes with subsequent therapy |
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