Serial minimal residual disease (MRD) monitoring during first-line FCR treatment for CLL may direct individualized therapeutic strategies
Achieving undetectable MRD (U-MRD) status after chemoimmunotherapy predicts longer progression-free and overall survival. The predictive factors and timing of relapse in patients with U-MRD and value of interim MRD analysis are ill-defined. This was a prospective study of 289 patients with CLL treat...
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| Veröffentlicht in: | Leukemia 2018-11, Vol.32 (11), p.2388-2398 |
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| creator | Thompson, Philip A. Peterson, Christine B. Strati, Paolo Jorgensen, Jeff Keating, Michael J. O’Brien, Susan M. Ferrajoli, Alessandra Burger, Jan A. Estrov, Zeev Jain, Nitin Kadia, Tapan M. Borthakur, Gautam DiNardo, Courtney D. Daver, Naval Jabbour, Elias Wierda, William G. |
| description | Achieving undetectable MRD (U-MRD) status after chemoimmunotherapy predicts longer progression-free and overall survival. The predictive factors and timing of relapse in patients with U-MRD and value of interim MRD analysis are ill-defined. This was a prospective study of 289 patients with CLL treated first-line with FCR. MRD analysis was performed after course 3 (C3) and at end of therapy (EOT) in bone marrow using 4-color flow cytometry (sensitivity 10
−4
). Eighteen percent of patients had U-MRD after C3 and 48% at EOT. U-MRD status at EOT was associated with longer PFS (median NR vs 38 mo,
p
1%) after C3 predicted greater likelihood of U-MRD status at EOT (64% vs 9%,
p
1% after C3 (median 73 mo vs 41 mo,
p
|
| doi_str_mv | 10.1038/s41375-018-0132-y |
| format | Article |
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−4
). Eighteen percent of patients had U-MRD after C3 and 48% at EOT. U-MRD status at EOT was associated with longer PFS (median NR vs 38 mo,
p
< 0.001). MRD level (≤1% vs >1%) after C3 predicted greater likelihood of U-MRD status at EOT (64% vs 9%,
p
< 0.001). PFS was significantly longer for patients with MRD ≤1% vs >1% after C3 (median 73 mo vs 41 mo,
p
< 0.001), but similar for <0.01% vs 0.01–1%. Interim MRD status may therefore be used for risk stratification and to individualize therapy. Eighty-five patients with U-MRD status at EOT had yearly blood MRD monitoring; MRD re-emerged in 38/85, a median of 48 mo after EOT and preceded clinical progression by a median of 24 months, which may allow development of early intervention strategies.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/s41375-018-0132-y</identifier><identifier>PMID: 29769624</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/31 ; 45/77 ; 631/67/1059/99 ; 631/67/1990/283/1895 ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Bone marrow ; Bone Marrow - drug effects ; Cancer Research ; Care and treatment ; Chronic lymphocytic leukemia ; Color sensitivity ; Critical Care Medicine ; Cyclophosphamide - administration & dosage ; Development and progression ; Disease-Free Survival ; Female ; Flow cytometry ; Genetic aspects ; Hematology ; Humans ; Immunotherapy ; Immunotherapy - methods ; Intensive ; Internal Medicine ; Leukemia ; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy ; Male ; Medical research ; Medical treatment ; Medicine ; Medicine & Public Health ; Middle Aged ; Minimal residual disease ; Monitoring ; Neoplasm, Residual - drug therapy ; Oncology ; Patient monitoring equipment ; Patients ; Prospective Studies ; Recurrence (Disease) ; Risk factors ; Rituximab - administration & dosage ; Therapy ; Vidarabine - administration & dosage ; Vidarabine - analogs & derivatives</subject><ispartof>Leukemia, 2018-11, Vol.32 (11), p.2388-2398</ispartof><rights>Macmillan Publishers Limited, part of Springer Nature 2018</rights><rights>COPYRIGHT 2018 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Nov 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c634t-b1dd5b09438e1e5ca7c52ad9704ad87b5f1d8d5b8a9c55be1e96ff68216b35273</citedby><cites>FETCH-LOGICAL-c634t-b1dd5b09438e1e5ca7c52ad9704ad87b5f1d8d5b8a9c55be1e96ff68216b35273</cites><orcidid>0000-0003-2086-6031 ; 0000-0002-9892-9832</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/s41375-018-0132-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41375-018-0132-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29769624$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thompson, Philip A.</creatorcontrib><creatorcontrib>Peterson, Christine B.</creatorcontrib><creatorcontrib>Strati, Paolo</creatorcontrib><creatorcontrib>Jorgensen, Jeff</creatorcontrib><creatorcontrib>Keating, Michael J.</creatorcontrib><creatorcontrib>O’Brien, Susan M.</creatorcontrib><creatorcontrib>Ferrajoli, Alessandra</creatorcontrib><creatorcontrib>Burger, Jan A.</creatorcontrib><creatorcontrib>Estrov, Zeev</creatorcontrib><creatorcontrib>Jain, Nitin</creatorcontrib><creatorcontrib>Kadia, Tapan M.</creatorcontrib><creatorcontrib>Borthakur, Gautam</creatorcontrib><creatorcontrib>DiNardo, Courtney D.</creatorcontrib><creatorcontrib>Daver, Naval</creatorcontrib><creatorcontrib>Jabbour, Elias</creatorcontrib><creatorcontrib>Wierda, William G.</creatorcontrib><title>Serial minimal residual disease (MRD) monitoring during first-line FCR treatment for CLL may direct individualized therapeutic strategies</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>Achieving undetectable MRD (U-MRD) status after chemoimmunotherapy predicts longer progression-free and overall survival. The predictive factors and timing of relapse in patients with U-MRD and value of interim MRD analysis are ill-defined. This was a prospective study of 289 patients with CLL treated first-line with FCR. MRD analysis was performed after course 3 (C3) and at end of therapy (EOT) in bone marrow using 4-color flow cytometry (sensitivity 10
−4
). Eighteen percent of patients had U-MRD after C3 and 48% at EOT. U-MRD status at EOT was associated with longer PFS (median NR vs 38 mo,
p
< 0.001). MRD level (≤1% vs >1%) after C3 predicted greater likelihood of U-MRD status at EOT (64% vs 9%,
p
< 0.001). PFS was significantly longer for patients with MRD ≤1% vs >1% after C3 (median 73 mo vs 41 mo,
p
< 0.001), but similar for <0.01% vs 0.01–1%. Interim MRD status may therefore be used for risk stratification and to individualize therapy. Eighty-five patients with U-MRD status at EOT had yearly blood MRD monitoring; MRD re-emerged in 38/85, a median of 48 mo after EOT and preceded clinical progression by a median of 24 months, which may allow development of early intervention strategies.</description><subject>13/31</subject><subject>45/77</subject><subject>631/67/1059/99</subject><subject>631/67/1990/283/1895</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Bone marrow</subject><subject>Bone Marrow - drug effects</subject><subject>Cancer Research</subject><subject>Care and treatment</subject><subject>Chronic lymphocytic leukemia</subject><subject>Color sensitivity</subject><subject>Critical Care Medicine</subject><subject>Cyclophosphamide - administration & dosage</subject><subject>Development and progression</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Genetic aspects</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Immunotherapy - methods</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Leukemia</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy</subject><subject>Male</subject><subject>Medical research</subject><subject>Medical treatment</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Minimal residual disease</subject><subject>Monitoring</subject><subject>Neoplasm, Residual - drug therapy</subject><subject>Oncology</subject><subject>Patient monitoring equipment</subject><subject>Patients</subject><subject>Prospective Studies</subject><subject>Recurrence (Disease)</subject><subject>Risk factors</subject><subject>Rituximab - administration & dosage</subject><subject>Therapy</subject><subject>Vidarabine - administration & dosage</subject><subject>Vidarabine - analogs & derivatives</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1ktFqFDEUhgdRbK0-gDcSEKReTE0yk2TmRiirVWFFqHodMsmZ3ZSZZJtkCusb-NZmurXuihLCCTnf-ZNz-IviOcFnBFfNm1iTSrASkybvipbbB8UxqQUvGWPkYXGMm0aUvKX1UfEkxiuM5yR_XBzRVvCW0_q4-PkVglUDGq2zY44BojVTPhgbQUVAp58v371Go3c2-WDdCpnpNvQ2xFQO1gG6WFyiFEClEVxCvQ9osVyiUW2zSACdkHXG3tzK2h9gUFpDUBuYktUopqASrCzEp8WjXg0Rnt3Fk-L7xftvi4_l8suHT4vzZal5VaeyI8awDrd11QABppXQjCrTClwr04iO9cQ0mWhUqxnrMtPyvucNJbyrGBXVSfF2p7uZuhGMzn8OapCbkPsPW-mVlYcZZ9dy5W8kJy1tBM4Cp3cCwV9PEJMcbdQwDMqBn6KkuMaCV4TN6Mu_0Cs_BZfbk5RUhFLetnvUSg0gret9flfPovKciYzVNeaZOvsHlZeB0WrvoLf5_qDg1V7BGtSQ1tEPeezexUOQ7EAdfIwB-vthECxno8md0WQ2mpyNJre55sX-FO8rfjsrA3QHxM3sFwh_Wv-_6i9gg98n</recordid><startdate>20181101</startdate><enddate>20181101</enddate><creator>Thompson, Philip A.</creator><creator>Peterson, Christine B.</creator><creator>Strati, Paolo</creator><creator>Jorgensen, Jeff</creator><creator>Keating, Michael J.</creator><creator>O’Brien, Susan M.</creator><creator>Ferrajoli, Alessandra</creator><creator>Burger, Jan A.</creator><creator>Estrov, Zeev</creator><creator>Jain, Nitin</creator><creator>Kadia, Tapan M.</creator><creator>Borthakur, Gautam</creator><creator>DiNardo, Courtney D.</creator><creator>Daver, Naval</creator><creator>Jabbour, Elias</creator><creator>Wierda, William G.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2086-6031</orcidid><orcidid>https://orcid.org/0000-0002-9892-9832</orcidid></search><sort><creationdate>20181101</creationdate><title>Serial minimal residual disease (MRD) monitoring during first-line FCR treatment for CLL may direct individualized therapeutic strategies</title><author>Thompson, Philip A. ; Peterson, Christine B. ; Strati, Paolo ; Jorgensen, Jeff ; Keating, Michael J. ; O’Brien, Susan M. ; Ferrajoli, Alessandra ; Burger, Jan A. ; Estrov, Zeev ; Jain, Nitin ; Kadia, Tapan M. ; Borthakur, Gautam ; DiNardo, Courtney D. ; Daver, Naval ; Jabbour, Elias ; Wierda, William G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c634t-b1dd5b09438e1e5ca7c52ad9704ad87b5f1d8d5b8a9c55be1e96ff68216b35273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>13/31</topic><topic>45/77</topic><topic>631/67/1059/99</topic><topic>631/67/1990/283/1895</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Bone marrow</topic><topic>Bone Marrow - drug effects</topic><topic>Cancer Research</topic><topic>Care and treatment</topic><topic>Chronic lymphocytic leukemia</topic><topic>Color sensitivity</topic><topic>Critical Care Medicine</topic><topic>Cyclophosphamide - administration & dosage</topic><topic>Development and progression</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Genetic aspects</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Immunotherapy - methods</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Leukemia</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy</topic><topic>Male</topic><topic>Medical research</topic><topic>Medical treatment</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Minimal residual disease</topic><topic>Monitoring</topic><topic>Neoplasm, Residual - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thompson, Philip A.</au><au>Peterson, Christine B.</au><au>Strati, Paolo</au><au>Jorgensen, Jeff</au><au>Keating, Michael J.</au><au>O’Brien, Susan M.</au><au>Ferrajoli, Alessandra</au><au>Burger, Jan A.</au><au>Estrov, Zeev</au><au>Jain, Nitin</au><au>Kadia, Tapan M.</au><au>Borthakur, Gautam</au><au>DiNardo, Courtney D.</au><au>Daver, Naval</au><au>Jabbour, Elias</au><au>Wierda, William G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serial minimal residual disease (MRD) monitoring during first-line FCR treatment for CLL may direct individualized therapeutic strategies</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2018-11-01</date><risdate>2018</risdate><volume>32</volume><issue>11</issue><spage>2388</spage><epage>2398</epage><pages>2388-2398</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>Achieving undetectable MRD (U-MRD) status after chemoimmunotherapy predicts longer progression-free and overall survival. The predictive factors and timing of relapse in patients with U-MRD and value of interim MRD analysis are ill-defined. This was a prospective study of 289 patients with CLL treated first-line with FCR. MRD analysis was performed after course 3 (C3) and at end of therapy (EOT) in bone marrow using 4-color flow cytometry (sensitivity 10
−4
). Eighteen percent of patients had U-MRD after C3 and 48% at EOT. U-MRD status at EOT was associated with longer PFS (median NR vs 38 mo,
p
< 0.001). MRD level (≤1% vs >1%) after C3 predicted greater likelihood of U-MRD status at EOT (64% vs 9%,
p
< 0.001). PFS was significantly longer for patients with MRD ≤1% vs >1% after C3 (median 73 mo vs 41 mo,
p
< 0.001), but similar for <0.01% vs 0.01–1%. Interim MRD status may therefore be used for risk stratification and to individualize therapy. Eighty-five patients with U-MRD status at EOT had yearly blood MRD monitoring; MRD re-emerged in 38/85, a median of 48 mo after EOT and preceded clinical progression by a median of 24 months, which may allow development of early intervention strategies.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29769624</pmid><doi>10.1038/s41375-018-0132-y</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-2086-6031</orcidid><orcidid>https://orcid.org/0000-0002-9892-9832</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2018-11, Vol.32 (11), p.2388-2398 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6192870 |
| source | MEDLINE; Springer Online Journals Complete; Nature Journals Online |
| subjects | 13/31 45/77 631/67/1059/99 631/67/1990/283/1895 Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bone marrow Bone Marrow - drug effects Cancer Research Care and treatment Chronic lymphocytic leukemia Color sensitivity Critical Care Medicine Cyclophosphamide - administration & dosage Development and progression Disease-Free Survival Female Flow cytometry Genetic aspects Hematology Humans Immunotherapy Immunotherapy - methods Intensive Internal Medicine Leukemia Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy Male Medical research Medical treatment Medicine Medicine & Public Health Middle Aged Minimal residual disease Monitoring Neoplasm, Residual - drug therapy Oncology Patient monitoring equipment Patients Prospective Studies Recurrence (Disease) Risk factors Rituximab - administration & dosage Therapy Vidarabine - administration & dosage Vidarabine - analogs & derivatives |
| title | Serial minimal residual disease (MRD) monitoring during first-line FCR treatment for CLL may direct individualized therapeutic strategies |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-12T14%3A50%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Serial%20minimal%20residual%20disease%20(MRD)%20monitoring%20during%20first-line%20FCR%20treatment%20for%20CLL%20may%20direct%20individualized%20therapeutic%20strategies&rft.jtitle=Leukemia&rft.au=Thompson,%20Philip%20A.&rft.date=2018-11-01&rft.volume=32&rft.issue=11&rft.spage=2388&rft.epage=2398&rft.pages=2388-2398&rft.issn=0887-6924&rft.eissn=1476-5551&rft_id=info:doi/10.1038/s41375-018-0132-y&rft_dat=%3Cgale_pubme%3EA573124406%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2131226990&rft_id=info:pmid/29769624&rft_galeid=A573124406&rfr_iscdi=true |