Impact of Minimal Residual Disease on Progression-Free Survival Outcomes after Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study

PURPOSEIn GLOW, fixed-duration ibrutinib + venetoclax showed superior progression-free survival (PFS) versus chlorambucil + obinutuzumab in older/comorbid patients with previously untreated chronic lymphocytic leukemia (CLL). The current analysis describes minimal residual disease (MRD) kinetics and...

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Autores: Munir, Talha|||0000-0002-2901-0769, Moreno, Carol|||0000-0003-3275-0271, Owen, Carolyn, Follows, George, Benjamini, Ohad, Janssens, Ann, Levin, Mark-David|||0000-0003-2139-3547, Osterborg, Anders, Robak, Tadeusz|||0000-0002-3411-6357, Simkovic, Martin|||0000-0003-0331-5334, Stevens, Don, Voloshin, Sergey, Vorobyev, Vladimir|||0000-0002-2692-8961, Yagci, Munci, Ysebaert, Loic|||0000-0003-4102-7261, Qi, Keqin|||0000-0002-8942-2888, Qi, Qianya, Parisi, Lori, Srinivasan, Srinivasan|||0000-0001-7202-9425, Schuier, Natasha, Baeten, Kurt, Howes, Angela, Caces, Donne Bennett, Niemann, Carsten U.|||0000-0001-9880-5242, Kater, Arnon P.|||0000-0003-3190-1891
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:289919
Acceso en línea:https://ddd.uab.cat/record/289919
https://dx.doi.org/urn:doi:10.1200/JCO.22.02283
Access Level:acceso abierto
Palabra clave:Aged
Antineoplastic Combined Chemotherapy Protocols
Bridged Bicyclo Compounds, Heterocyclic
Chlorambucil
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasm, Residual
Progression-Free Survival
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repository_id_str
spelling Impact of Minimal Residual Disease on Progression-Free Survival Outcomes after Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW StudyMunir, Talha|||0000-0002-2901-0769Moreno, Carol|||0000-0003-3275-0271Owen, CarolynFollows, GeorgeBenjamini, OhadJanssens, AnnLevin, Mark-David|||0000-0003-2139-3547Osterborg, AndersRobak, Tadeusz|||0000-0002-3411-6357Simkovic, Martin|||0000-0003-0331-5334Stevens, DonVoloshin, SergeyVorobyev, Vladimir|||0000-0002-2692-8961Yagci, MunciYsebaert, Loic|||0000-0003-4102-7261Qi, Keqin|||0000-0002-8942-2888Qi, QianyaParisi, LoriSrinivasan, Srinivasan|||0000-0001-7202-9425Schuier, NatashaBaeten, KurtHowes, AngelaCaces, Donne BennettNiemann, Carsten U.|||0000-0001-9880-5242Kater, Arnon P.|||0000-0003-3190-1891AgedAntineoplastic Combined Chemotherapy ProtocolsBridged Bicyclo Compounds, HeterocyclicChlorambucilHumansLeukemia, Lymphocytic, Chronic, B-CellNeoplasm, ResidualProgression-Free SurvivalPURPOSEIn GLOW, fixed-duration ibrutinib + venetoclax showed superior progression-free survival (PFS) versus chlorambucil + obinutuzumab in older/comorbid patients with previously untreated chronic lymphocytic leukemia (CLL). The current analysis describes minimal residual disease (MRD) kinetics and any potential predictive value for PFS, as it has not yet been evaluated for ibrutinib + venetoclax treatment.METHODSUndetectable MRD (uMRD) was assessed by next-generation sequencing at <1 CLL cell per 10,000 (<10-4) and <1 CLL cell per 100,000 (<10-5) leukocytes. PFS was analyzed by MRD status at 3 months after treatment (EOT+3).RESULTSIbrutinib + venetoclax achieved deeper uMRD (<10-5) rates in bone marrow (BM) and peripheral blood (PB), respectively, in 40.6% and 43.4% of patients at EOT+3 versus 7.6% and 18.1% of patients receiving chlorambucil + obinutuzumab. Of these patients, uMRD (<10-5) in PB was sustained during the first year post-treatment (EOT+12) in 80.4% of patients receiving ibrutinib + venetoclax and 26.3% receiving chlorambucil + obinutuzumab. Patients with detectable MRD (dMRD; ≥10-4) in PB at EOT+3 were more likely to sustain MRD levels through EOT+12 with ibrutinib + venetoclax versus chlorambucil + obinutuzumab. PFS rates at EOT+12 were high among patients treated with ibrutinib + venetoclax regardless of MRD status at EOT+3: 96.3% and 93.3% in patients with uMRD (<10-4) and dMRD (≥10-4) in BM, respectively, versus 83.3% and 58.7% for patients receiving chlorambucil + obinutuzumab. PFS rates at EOT+12 also remained high in patients with unmutated immunoglobulin heavy-chain variable region (IGHV) receiving ibrutinib + venetoclax, independent of MRD status in BM.CONCLUSIONMolecular and clinical relapses were less frequent during the first year post-treatment with ibrutinib + venetoclax versus chlorambucil + obinutuzumab regardless of MRD status at EOT+3 and IGHV status. Even for patients not achieving uMRD (<10-4), PFS rates remained high with ibrutinib + venetoclax; this is a novel finding and requires additional follow-up to confirm its persistence over time. 22023-01-0120232023-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/289919https://dx.doi.org/urn:doi:10.1200/JCO.22.02283reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2899192026-06-06T12:50:31Z
dc.title.none.fl_str_mv Impact of Minimal Residual Disease on Progression-Free Survival Outcomes after Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study
title Impact of Minimal Residual Disease on Progression-Free Survival Outcomes after Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study
spellingShingle Impact of Minimal Residual Disease on Progression-Free Survival Outcomes after Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study
Munir, Talha|||0000-0002-2901-0769
Aged
Antineoplastic Combined Chemotherapy Protocols
Bridged Bicyclo Compounds, Heterocyclic
Chlorambucil
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasm, Residual
Progression-Free Survival
title_short Impact of Minimal Residual Disease on Progression-Free Survival Outcomes after Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study
title_full Impact of Minimal Residual Disease on Progression-Free Survival Outcomes after Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study
title_fullStr Impact of Minimal Residual Disease on Progression-Free Survival Outcomes after Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study
title_full_unstemmed Impact of Minimal Residual Disease on Progression-Free Survival Outcomes after Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study
title_sort Impact of Minimal Residual Disease on Progression-Free Survival Outcomes after Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study
dc.creator.none.fl_str_mv Munir, Talha|||0000-0002-2901-0769
Moreno, Carol|||0000-0003-3275-0271
Owen, Carolyn
Follows, George
Benjamini, Ohad
Janssens, Ann
Levin, Mark-David|||0000-0003-2139-3547
Osterborg, Anders
Robak, Tadeusz|||0000-0002-3411-6357
Simkovic, Martin|||0000-0003-0331-5334
Stevens, Don
Voloshin, Sergey
Vorobyev, Vladimir|||0000-0002-2692-8961
Yagci, Munci
Ysebaert, Loic|||0000-0003-4102-7261
Qi, Keqin|||0000-0002-8942-2888
Qi, Qianya
Parisi, Lori
Srinivasan, Srinivasan|||0000-0001-7202-9425
Schuier, Natasha
Baeten, Kurt
Howes, Angela
Caces, Donne Bennett
Niemann, Carsten U.|||0000-0001-9880-5242
Kater, Arnon P.|||0000-0003-3190-1891
author Munir, Talha|||0000-0002-2901-0769
author_facet Munir, Talha|||0000-0002-2901-0769
Moreno, Carol|||0000-0003-3275-0271
Owen, Carolyn
Follows, George
Benjamini, Ohad
Janssens, Ann
Levin, Mark-David|||0000-0003-2139-3547
Osterborg, Anders
Robak, Tadeusz|||0000-0002-3411-6357
Simkovic, Martin|||0000-0003-0331-5334
Stevens, Don
Voloshin, Sergey
Vorobyev, Vladimir|||0000-0002-2692-8961
Yagci, Munci
Ysebaert, Loic|||0000-0003-4102-7261
Qi, Keqin|||0000-0002-8942-2888
Qi, Qianya
Parisi, Lori
Srinivasan, Srinivasan|||0000-0001-7202-9425
Schuier, Natasha
Baeten, Kurt
Howes, Angela
Caces, Donne Bennett
Niemann, Carsten U.|||0000-0001-9880-5242
Kater, Arnon P.|||0000-0003-3190-1891
author_role author
author2 Moreno, Carol|||0000-0003-3275-0271
Owen, Carolyn
Follows, George
Benjamini, Ohad
Janssens, Ann
Levin, Mark-David|||0000-0003-2139-3547
Osterborg, Anders
Robak, Tadeusz|||0000-0002-3411-6357
Simkovic, Martin|||0000-0003-0331-5334
Stevens, Don
Voloshin, Sergey
Vorobyev, Vladimir|||0000-0002-2692-8961
Yagci, Munci
Ysebaert, Loic|||0000-0003-4102-7261
Qi, Keqin|||0000-0002-8942-2888
Qi, Qianya
Parisi, Lori
Srinivasan, Srinivasan|||0000-0001-7202-9425
Schuier, Natasha
Baeten, Kurt
Howes, Angela
Caces, Donne Bennett
Niemann, Carsten U.|||0000-0001-9880-5242
Kater, Arnon P.|||0000-0003-3190-1891
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Aged
Antineoplastic Combined Chemotherapy Protocols
Bridged Bicyclo Compounds, Heterocyclic
Chlorambucil
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasm, Residual
Progression-Free Survival
topic Aged
Antineoplastic Combined Chemotherapy Protocols
Bridged Bicyclo Compounds, Heterocyclic
Chlorambucil
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasm, Residual
Progression-Free Survival
description PURPOSEIn GLOW, fixed-duration ibrutinib + venetoclax showed superior progression-free survival (PFS) versus chlorambucil + obinutuzumab in older/comorbid patients with previously untreated chronic lymphocytic leukemia (CLL). The current analysis describes minimal residual disease (MRD) kinetics and any potential predictive value for PFS, as it has not yet been evaluated for ibrutinib + venetoclax treatment.METHODSUndetectable MRD (uMRD) was assessed by next-generation sequencing at <1 CLL cell per 10,000 (<10-4) and <1 CLL cell per 100,000 (<10-5) leukocytes. PFS was analyzed by MRD status at 3 months after treatment (EOT+3).RESULTSIbrutinib + venetoclax achieved deeper uMRD (<10-5) rates in bone marrow (BM) and peripheral blood (PB), respectively, in 40.6% and 43.4% of patients at EOT+3 versus 7.6% and 18.1% of patients receiving chlorambucil + obinutuzumab. Of these patients, uMRD (<10-5) in PB was sustained during the first year post-treatment (EOT+12) in 80.4% of patients receiving ibrutinib + venetoclax and 26.3% receiving chlorambucil + obinutuzumab. Patients with detectable MRD (dMRD; ≥10-4) in PB at EOT+3 were more likely to sustain MRD levels through EOT+12 with ibrutinib + venetoclax versus chlorambucil + obinutuzumab. PFS rates at EOT+12 were high among patients treated with ibrutinib + venetoclax regardless of MRD status at EOT+3: 96.3% and 93.3% in patients with uMRD (<10-4) and dMRD (≥10-4) in BM, respectively, versus 83.3% and 58.7% for patients receiving chlorambucil + obinutuzumab. PFS rates at EOT+12 also remained high in patients with unmutated immunoglobulin heavy-chain variable region (IGHV) receiving ibrutinib + venetoclax, independent of MRD status in BM.CONCLUSIONMolecular and clinical relapses were less frequent during the first year post-treatment with ibrutinib + venetoclax versus chlorambucil + obinutuzumab regardless of MRD status at EOT+3 and IGHV status. Even for patients not achieving uMRD (<10-4), PFS rates remained high with ibrutinib + venetoclax; this is a novel finding and requires additional follow-up to confirm its persistence over time.
publishDate 2023
dc.date.none.fl_str_mv 2
2023-01-01
2023
2023-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/289919
https://dx.doi.org/urn:doi:10.1200/JCO.22.02283
url https://ddd.uab.cat/record/289919
https://dx.doi.org/urn:doi:10.1200/JCO.22.02283
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
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