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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| Format: | Article |
| Publication date: | 2023 |
| Country: | España |
| Institution: | Universitat Autònoma de Barcelona |
| Repository: | Dipòsit Digital de Documents de la UAB |
| Language: | English |
| OAI Identifier: | oai:ddd.uab.cat:289919 |
| Online Access: | https://ddd.uab.cat/record/289919 https://dx.doi.org/urn:doi:10.1200/JCO.22.02283 |
| Access Level: | Open access |
| Keyword: | Aged Antineoplastic Combined Chemotherapy Protocols Bridged Bicyclo Compounds, Heterocyclic Chlorambucil Humans Leukemia, Lymphocytic, Chronic, B-Cell Neoplasm, Residual Progression-Free Survival |
| _version_ | 1878738108393979904 |
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| author | Munir, Talha|||0000-0002-2901-0769 |
| 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 |
| author_browse | Baeten, Kurt Benjamini, Ohad Caces, Donne Bennett Follows, George Howes, Angela Janssens, Ann Kater, Arnon P.|||0000-0003-3190-1891 Levin, Mark-David|||0000-0003-2139-3547 Moreno, Carol|||0000-0003-3275-0271 Munir, Talha|||0000-0002-2901-0769 Niemann, Carsten U.|||0000-0001-9880-5242 Osterborg, Anders Owen, Carolyn Parisi, Lori Qi, Keqin|||0000-0002-8942-2888 Qi, Qianya Robak, Tadeusz|||0000-0002-3411-6357 Schuier, Natasha Simkovic, Martin|||0000-0003-0331-5334 Srinivasan, Srinivasan|||0000-0001-7202-9425 Stevens, Don Voloshin, Sergey Vorobyev, Vladimir|||0000-0002-2692-8961 Yagci, Munci Ysebaert, Loic|||0000-0003-4102-7261 |
| 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 |
| collection | Dipòsit Digital de Documents de la UAB |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_a9bfd95d596a8a90e7e1c328dffbe5bf |
| institution | Universitat Autònoma de Barcelona |
| instname_str | Universitat Autònoma de Barcelona |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:ddd.uab.cat:289919 |
| publishDate | 2023 |
| publishDateSort | 2023 |
| reponame_str | Dipòsit Digital de Documents de la UAB |
| spelling | 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 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 Aged Antineoplastic Combined Chemotherapy Protocols Bridged Bicyclo Compounds, Heterocyclic Chlorambucil Humans Leukemia, Lymphocytic, Chronic, B-Cell Neoplasm, Residual Progression-Free Survival 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. https://ddd.uab.cat/record/289919 https://dx.doi.org/urn:doi:10.1200/JCO.22.02283 |
| 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 | 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_short | 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 |
| topic | Aged Antineoplastic Combined Chemotherapy Protocols Bridged Bicyclo Compounds, Heterocyclic Chlorambucil Humans Leukemia, Lymphocytic, Chronic, B-Cell Neoplasm, Residual Progression-Free Survival |
| topic_facet | Aged Antineoplastic Combined Chemotherapy Protocols Bridged Bicyclo Compounds, Heterocyclic Chlorambucil Humans Leukemia, Lymphocytic, Chronic, B-Cell Neoplasm, Residual Progression-Free Survival |
| url | https://ddd.uab.cat/record/289919 https://dx.doi.org/urn:doi:10.1200/JCO.22.02283 |