Incidences of Deep Molecular Responses and Treatment-Free Remission in de Novo CP-CML Patients

Background: Tyrosine Kinase Inhibitors (TKIs) discontinuation in patients who had achieved a deep molecular response (DMR) offer now the opportunity of prolonged treatment-free remission (TFR). Patients and Methods: Aims of this study were to evaluate the proportion of de novo chronic-phase chronic...

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Veröffentlicht in:Cancers 2020-09, Vol.12 (9), p.2521
Hauptverfasser: Etienne, Gabriel, Dulucq, Stéphanie, Bauduer, Fréderic, Adiko, Didier, Lifermann, François, Dagada, Corinne, Lenoir, Caroline, Schmitt, Anna, Klein, Emilie, Madene, Samia, Fort, Marie-Pierre, Bijou, Fontanet, Moldovan, Marius, Turcq, Beatrice, Robbesyn, Fanny, Durrieu, Françoise, Versmée, Laura, Katsahian, Sandrine, Faberes, Carole, Lascaux, Axelle, Mahon, François-Xavier
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container_end_page
container_issue 9
container_start_page 2521
container_title Cancers
container_volume 12
creator Etienne, Gabriel
Dulucq, Stéphanie
Bauduer, Fréderic
Adiko, Didier
Lifermann, François
Dagada, Corinne
Lenoir, Caroline
Schmitt, Anna
Klein, Emilie
Madene, Samia
Fort, Marie-Pierre
Bijou, Fontanet
Moldovan, Marius
Turcq, Beatrice
Robbesyn, Fanny
Durrieu, Françoise
Versmée, Laura
Katsahian, Sandrine
Faberes, Carole
Lascaux, Axelle
Mahon, François-Xavier
description Background: Tyrosine Kinase Inhibitors (TKIs) discontinuation in patients who had achieved a deep molecular response (DMR) offer now the opportunity of prolonged treatment-free remission (TFR). Patients and Methods: Aims of this study were to evaluate the proportion of de novo chronic-phase chronic myeloid leukemia (CP-CML) patients who achieved a sustained DMR and to identify predictive factors of DMR and molecular recurrence-free survival (MRFS) after TKI discontinuation. Results: Over a period of 10 years, 398 CP-CML patients treated with first-line TKIs were included. Median age at diagnosis was 61 years, 291 (73%) and 107 (27%) patients were treated with frontline imatinib (IMA) or second- or third-generation TKIs (2–3G TKI), respectively. With a median follow-up of seven years (range, 0.6 to 13.8 years), 182 (46%) patients achieved a sustained DMR at least 24 months. Gender, BCR-ABL1 transcript type, and Sokal and ELTS risk scores were significantly associated with a higher probability of sustained DMR while TKI first-line (IMA vs. 2–3G TKI) was not. We estimate that 28% of CML-CP would have been an optimal candidate for TKI discontinuation according to recent recommendations. Finally, 95 (24%) patients have entered in a TFR program. MRFS rates at 12 and 48 months were 55.1% (95% CI, 44.3% to 65.9%) and 46.9% (95% CI, 34.9% to 58.9%), respectively. In multivariate analyses, first-line 2–3G TKIs compared to IMA and TKI duration were the most significant factors of MRFS. Conclusions: Our results suggest that frontline TKIs have a significant impact on TFR in patients who fulfill the selection criteria for TKI discontinuation.
doi_str_mv 10.3390/cancers12092521
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fullrecord <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7565328</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A638189995</galeid><sourcerecordid>A638189995</sourcerecordid><originalsourceid>FETCH-LOGICAL-c460t-638933f2ecc0ff6135f4a73ccfc02e480700bd848b4a29e7e6e3ab55f369944f3</originalsourceid><addsrcrecordid>eNpdkktPGzEUhUdVq4KANVtL3bSLAb8fm0pRKAUptKii21qO5xoGTezUnonUf1-HIFrijS2fz-deHd-mOSX4jDGDz72LHnIhFBsqKHnTHFKsaCul4W__Ox80J6U84roYI0qq980Bo9oYrcxh8-s6-r6DalRQCugCYI1u0gB-GlxGP6CsUyxVc7FDdxncuII4tpcZoIqrvpQ-RdRH1AH6ljYJzW_b-c0C3bqxr2A5bt4FNxQ4ed6Pmp-XX-7mV-3i-9fr-WzRei7x2EqmDWOBgvc4BEmYCNwp5n3wmALXWGG87DTXS-6oAQUSmFsKEZg0hvPAjprPO9_1tFxB52vt7Aa7zv3K5T82ud6-VmL_YO_TxiohRU2jGnzaGTzsPbuaLez2DjOsBTF6Qyr78blYTr8nKKOtQXgYBhchTcVSzgnV2AhR0Q976GOacqxRPFHYKEHwP-reDWD7GFLt0W9N7axGQ-pnma3X-Y7yOZWSIbz0SbDdDoTdGwj2F4UkpiE</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2441097510</pqid></control><display><type>article</type><title>Incidences of Deep Molecular Responses and Treatment-Free Remission in de Novo CP-CML Patients</title><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Etienne, Gabriel ; Dulucq, Stéphanie ; Bauduer, Fréderic ; Adiko, Didier ; Lifermann, François ; Dagada, Corinne ; Lenoir, Caroline ; Schmitt, Anna ; Klein, Emilie ; Madene, Samia ; Fort, Marie-Pierre ; Bijou, Fontanet ; Moldovan, Marius ; Turcq, Beatrice ; Robbesyn, Fanny ; Durrieu, Françoise ; Versmée, Laura ; Katsahian, Sandrine ; Faberes, Carole ; Lascaux, Axelle ; Mahon, François-Xavier</creator><creatorcontrib>Etienne, Gabriel ; Dulucq, Stéphanie ; Bauduer, Fréderic ; Adiko, Didier ; Lifermann, François ; Dagada, Corinne ; Lenoir, Caroline ; Schmitt, Anna ; Klein, Emilie ; Madene, Samia ; Fort, Marie-Pierre ; Bijou, Fontanet ; Moldovan, Marius ; Turcq, Beatrice ; Robbesyn, Fanny ; Durrieu, Françoise ; Versmée, Laura ; Katsahian, Sandrine ; Faberes, Carole ; Lascaux, Axelle ; Mahon, François-Xavier</creatorcontrib><description>Background: Tyrosine Kinase Inhibitors (TKIs) discontinuation in patients who had achieved a deep molecular response (DMR) offer now the opportunity of prolonged treatment-free remission (TFR). Patients and Methods: Aims of this study were to evaluate the proportion of de novo chronic-phase chronic myeloid leukemia (CP-CML) patients who achieved a sustained DMR and to identify predictive factors of DMR and molecular recurrence-free survival (MRFS) after TKI discontinuation. Results: Over a period of 10 years, 398 CP-CML patients treated with first-line TKIs were included. Median age at diagnosis was 61 years, 291 (73%) and 107 (27%) patients were treated with frontline imatinib (IMA) or second- or third-generation TKIs (2–3G TKI), respectively. With a median follow-up of seven years (range, 0.6 to 13.8 years), 182 (46%) patients achieved a sustained DMR at least 24 months. Gender, BCR-ABL1 transcript type, and Sokal and ELTS risk scores were significantly associated with a higher probability of sustained DMR while TKI first-line (IMA vs. 2–3G TKI) was not. We estimate that 28% of CML-CP would have been an optimal candidate for TKI discontinuation according to recent recommendations. Finally, 95 (24%) patients have entered in a TFR program. MRFS rates at 12 and 48 months were 55.1% (95% CI, 44.3% to 65.9%) and 46.9% (95% CI, 34.9% to 58.9%), respectively. In multivariate analyses, first-line 2–3G TKIs compared to IMA and TKI duration were the most significant factors of MRFS. Conclusions: Our results suggest that frontline TKIs have a significant impact on TFR in patients who fulfill the selection criteria for TKI discontinuation.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers12092521</identifier><identifier>PMID: 32899879</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Chronic myeloid leukemia ; Clinical trials ; Disease ; Dosage and administration ; Drug therapy ; Imatinib ; Kinase inhibitors ; Kinases ; Leukemia ; Life Sciences ; Medical prognosis ; Myeloid leukemia ; Patient outcomes ; Protein-tyrosine kinase ; Remission ; Transcription</subject><ispartof>Cancers, 2020-09, Vol.12 (9), p.2521</ispartof><rights>COPYRIGHT 2020 MDPI AG</rights><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c460t-638933f2ecc0ff6135f4a73ccfc02e480700bd848b4a29e7e6e3ab55f369944f3</citedby><cites>FETCH-LOGICAL-c460t-638933f2ecc0ff6135f4a73ccfc02e480700bd848b4a29e7e6e3ab55f369944f3</cites><orcidid>0000-0002-7687-3743 ; 0000-0002-0481-2909 ; 0000-0002-5423-0552 ; 0000-0001-6768-7175 ; 0000-0002-0246-0866 ; 0000-0003-2235-8540 ; 0000-0003-2728-7243 ; 0000-0002-7261-0671 ; 0000-0001-7600-4954 ; 0000-0002-4983-5581</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/PMC7565328/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565328/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://hal.science/hal-03085198$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Etienne, Gabriel</creatorcontrib><creatorcontrib>Dulucq, Stéphanie</creatorcontrib><creatorcontrib>Bauduer, Fréderic</creatorcontrib><creatorcontrib>Adiko, Didier</creatorcontrib><creatorcontrib>Lifermann, François</creatorcontrib><creatorcontrib>Dagada, Corinne</creatorcontrib><creatorcontrib>Lenoir, Caroline</creatorcontrib><creatorcontrib>Schmitt, Anna</creatorcontrib><creatorcontrib>Klein, Emilie</creatorcontrib><creatorcontrib>Madene, Samia</creatorcontrib><creatorcontrib>Fort, Marie-Pierre</creatorcontrib><creatorcontrib>Bijou, Fontanet</creatorcontrib><creatorcontrib>Moldovan, Marius</creatorcontrib><creatorcontrib>Turcq, Beatrice</creatorcontrib><creatorcontrib>Robbesyn, Fanny</creatorcontrib><creatorcontrib>Durrieu, Françoise</creatorcontrib><creatorcontrib>Versmée, Laura</creatorcontrib><creatorcontrib>Katsahian, Sandrine</creatorcontrib><creatorcontrib>Faberes, Carole</creatorcontrib><creatorcontrib>Lascaux, Axelle</creatorcontrib><creatorcontrib>Mahon, François-Xavier</creatorcontrib><title>Incidences of Deep Molecular Responses and Treatment-Free Remission in de Novo CP-CML Patients</title><title>Cancers</title><description>Background: Tyrosine Kinase Inhibitors (TKIs) discontinuation in patients who had achieved a deep molecular response (DMR) offer now the opportunity of prolonged treatment-free remission (TFR). Patients and Methods: Aims of this study were to evaluate the proportion of de novo chronic-phase chronic myeloid leukemia (CP-CML) patients who achieved a sustained DMR and to identify predictive factors of DMR and molecular recurrence-free survival (MRFS) after TKI discontinuation. Results: Over a period of 10 years, 398 CP-CML patients treated with first-line TKIs were included. Median age at diagnosis was 61 years, 291 (73%) and 107 (27%) patients were treated with frontline imatinib (IMA) or second- or third-generation TKIs (2–3G TKI), respectively. With a median follow-up of seven years (range, 0.6 to 13.8 years), 182 (46%) patients achieved a sustained DMR at least 24 months. Gender, BCR-ABL1 transcript type, and Sokal and ELTS risk scores were significantly associated with a higher probability of sustained DMR while TKI first-line (IMA vs. 2–3G TKI) was not. 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inhibitors</topic><topic>Kinases</topic><topic>Leukemia</topic><topic>Life Sciences</topic><topic>Medical prognosis</topic><topic>Myeloid leukemia</topic><topic>Patient outcomes</topic><topic>Protein-tyrosine kinase</topic><topic>Remission</topic><topic>Transcription</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Etienne, Gabriel</creatorcontrib><creatorcontrib>Dulucq, Stéphanie</creatorcontrib><creatorcontrib>Bauduer, Fréderic</creatorcontrib><creatorcontrib>Adiko, Didier</creatorcontrib><creatorcontrib>Lifermann, François</creatorcontrib><creatorcontrib>Dagada, Corinne</creatorcontrib><creatorcontrib>Lenoir, Caroline</creatorcontrib><creatorcontrib>Schmitt, Anna</creatorcontrib><creatorcontrib>Klein, Emilie</creatorcontrib><creatorcontrib>Madene, Samia</creatorcontrib><creatorcontrib>Fort, Marie-Pierre</creatorcontrib><creatorcontrib>Bijou, Fontanet</creatorcontrib><creatorcontrib>Moldovan, Marius</creatorcontrib><creatorcontrib>Turcq, 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Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Etienne, Gabriel</au><au>Dulucq, Stéphanie</au><au>Bauduer, Fréderic</au><au>Adiko, Didier</au><au>Lifermann, François</au><au>Dagada, Corinne</au><au>Lenoir, Caroline</au><au>Schmitt, Anna</au><au>Klein, Emilie</au><au>Madene, Samia</au><au>Fort, Marie-Pierre</au><au>Bijou, Fontanet</au><au>Moldovan, Marius</au><au>Turcq, Beatrice</au><au>Robbesyn, Fanny</au><au>Durrieu, Françoise</au><au>Versmée, Laura</au><au>Katsahian, Sandrine</au><au>Faberes, Carole</au><au>Lascaux, Axelle</au><au>Mahon, François-Xavier</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Incidences of Deep Molecular Responses and Treatment-Free Remission in de Novo CP-CML Patients</atitle><jtitle>Cancers</jtitle><date>2020-09-01</date><risdate>2020</risdate><volume>12</volume><issue>9</issue><spage>2521</spage><pages>2521-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Background: Tyrosine Kinase Inhibitors (TKIs) discontinuation in patients who had achieved a deep molecular response (DMR) offer now the opportunity of prolonged treatment-free remission (TFR). Patients and Methods: Aims of this study were to evaluate the proportion of de novo chronic-phase chronic myeloid leukemia (CP-CML) patients who achieved a sustained DMR and to identify predictive factors of DMR and molecular recurrence-free survival (MRFS) after TKI discontinuation. Results: Over a period of 10 years, 398 CP-CML patients treated with first-line TKIs were included. Median age at diagnosis was 61 years, 291 (73%) and 107 (27%) patients were treated with frontline imatinib (IMA) or second- or third-generation TKIs (2–3G TKI), respectively. With a median follow-up of seven years (range, 0.6 to 13.8 years), 182 (46%) patients achieved a sustained DMR at least 24 months. Gender, BCR-ABL1 transcript type, and Sokal and ELTS risk scores were significantly associated with a higher probability of sustained DMR while TKI first-line (IMA vs. 2–3G TKI) was not. We estimate that 28% of CML-CP would have been an optimal candidate for TKI discontinuation according to recent recommendations. Finally, 95 (24%) patients have entered in a TFR program. MRFS rates at 12 and 48 months were 55.1% (95% CI, 44.3% to 65.9%) and 46.9% (95% CI, 34.9% to 58.9%), respectively. In multivariate analyses, first-line 2–3G TKIs compared to IMA and TKI duration were the most significant factors of MRFS. Conclusions: Our results suggest that frontline TKIs have a significant impact on TFR in patients who fulfill the selection criteria for TKI discontinuation.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>32899879</pmid><doi>10.3390/cancers12092521</doi><orcidid>https://orcid.org/0000-0002-7687-3743</orcidid><orcidid>https://orcid.org/0000-0002-0481-2909</orcidid><orcidid>https://orcid.org/0000-0002-5423-0552</orcidid><orcidid>https://orcid.org/0000-0001-6768-7175</orcidid><orcidid>https://orcid.org/0000-0002-0246-0866</orcidid><orcidid>https://orcid.org/0000-0003-2235-8540</orcidid><orcidid>https://orcid.org/0000-0003-2728-7243</orcidid><orcidid>https://orcid.org/0000-0002-7261-0671</orcidid><orcidid>https://orcid.org/0000-0001-7600-4954</orcidid><orcidid>https://orcid.org/0000-0002-4983-5581</orcidid><oa>free_for_read</oa></addata></record>
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source MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access
subjects Chronic myeloid leukemia
Clinical trials
Disease
Dosage and administration
Drug therapy
Imatinib
Kinase inhibitors
Kinases
Leukemia
Life Sciences
Medical prognosis
Myeloid leukemia
Patient outcomes
Protein-tyrosine kinase
Remission
Transcription
title Incidences of Deep Molecular Responses and Treatment-Free Remission in de Novo CP-CML Patients
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T01%3A57%3A52IST&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=Incidences%20of%20Deep%20Molecular%20Responses%20and%20Treatment-Free%20Remission%20in%20de%20Novo%20CP-CML%20Patients&rft.jtitle=Cancers&rft.au=Etienne,%20Gabriel&rft.date=2020-09-01&rft.volume=12&rft.issue=9&rft.spage=2521&rft.pages=2521-&rft.issn=2072-6694&rft.eissn=2072-6694&rft_id=info:doi/10.3390/cancers12092521&rft_dat=%3Cgale_pubme%3EA638189995%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=2441097510&rft_id=info:pmid/32899879&rft_galeid=A638189995&rfr_iscdi=true