Long-term follow-up of MRD-guided ibrutinib plus venetoclax in relapsed CLL: phase 2 VISION/HO141 trial
Abstract: Patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) are treated with fixed-duration B-cell lymphoma 2 inhibitors + CD20 monoclonal antibodies or continuous Bruton tyrosine kinase (BTK) inhibitors. Although continuous treatment may lead to cumulative toxicity or resis...
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Elsevier
2025-08-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952925002381 |
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| author | Carsten U. Niemann Julie Dubois Kazem Nasserinejad Caspar da Cunha-Bang Sabina Kersting Lisbeth Enggaard Gerrit J. Veldhuis Rogier Mous Clemens H.M. Mellink Anne-Marie F. van der Kevie-Kersemaekers Johan A. Dobber Christian B. Poulsen Wida Razawy René Hollestein Henrik Frederiksen Ann Janssens Ida Schjødt Ellen C. Dompeling Juha Ranti Christian Brieghel Mattias Mattsson Mar Bellido Hoa T. T. Tran Arnon P. Kater Mark-David Levin |
| author_facet | Carsten U. Niemann Julie Dubois Kazem Nasserinejad Caspar da Cunha-Bang Sabina Kersting Lisbeth Enggaard Gerrit J. Veldhuis Rogier Mous Clemens H.M. Mellink Anne-Marie F. van der Kevie-Kersemaekers Johan A. Dobber Christian B. Poulsen Wida Razawy René Hollestein Henrik Frederiksen Ann Janssens Ida Schjødt Ellen C. Dompeling Juha Ranti Christian Brieghel Mattias Mattsson Mar Bellido Hoa T. T. Tran Arnon P. Kater Mark-David Levin |
| author_sort | Carsten U. Niemann |
| collection | DOAJ |
| description | Abstract: Patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) are treated with fixed-duration B-cell lymphoma 2 inhibitors + CD20 monoclonal antibodies or continuous Bruton tyrosine kinase (BTK) inhibitors. Although continuous treatment may lead to cumulative toxicity or resistance, fixed-duration treatment may lead to undertreatment and early relapse. Efficacy and safety of minimal residual disease (MRD)-guided treatment cessation of ibrutinib + venetoclax (I+V) with reinitiated I+V upon MRD conversion was evaluated in the randomized VISION/HO41 phase 2 study. Four-year follow-up including long-term toxicity and MRD kinetics are reported. Patients received ibrutinib for 2 (28-day) cycles followed by 13 cycles of I+V. Patients reaching undetectable MRD at 4 years (<10−4, flow cytometry) in the blood and bone marrow at cycle 15 (C15) were randomized 2:1 between treatment cessation with reinitiated I+V upon detectable MRD2 (dMRD2; sensitivity of ≥10−2 by flow cytometry) and ibrutinib maintenance. MRD4-positive patients at C15 remained on ibrutinib (dMRD4 arm, defined by MRD sensitivity of ≥10−4 by flow cytometry). With a median of 51.7 months, the estimated 4-year overall survival (OS) was 88%, progression free survival (PFS) was 81%; 14% of patients required next-line treatment (NT). For patients randomized to treatment cessation, 40% had reinitiated therapy per protocol because of dMRD2. No difference between treatment cessation, ibrutinib maintenance, or the dMRD4 arm continuing ibrutinib was seen for OS, PFS, or NT in landmark analysis from C15 time of randomization. Lower toxicity was demonstrated for the treatment-cessation arm. MRD-guided cessation and reinitiation of I+V for R/R CLL is feasible, reduces toxicity compared with indefinite BTK inhibitor, while providing comparable PFS rates. This trial was registered at www.clinicaltrials.gov as #NCT03226301. |
| format | Article |
| id | doaj-art-781b8353fcdd42d1b9db6f0cfd064aaa |
| institution | Kabale University |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-781b8353fcdd42d1b9db6f0cfd064aaa2025-08-20T03:55:53ZengElsevierBlood Advances2473-95292025-08-019153665367510.1182/bloodadvances.2024015180Long-term follow-up of MRD-guided ibrutinib plus venetoclax in relapsed CLL: phase 2 VISION/HO141 trialCarsten U. Niemann0Julie Dubois1Kazem Nasserinejad2Caspar da Cunha-Bang3Sabina Kersting4Lisbeth Enggaard5Gerrit J. Veldhuis6Rogier Mous7Clemens H.M. Mellink8Anne-Marie F. van der Kevie-Kersemaekers9Johan A. Dobber10Christian B. Poulsen11Wida Razawy12René Hollestein13Henrik Frederiksen14Ann Janssens15Ida Schjødt16Ellen C. Dompeling17Juha Ranti18Christian Brieghel19Mattias Mattsson20Mar Bellido21Hoa T. T. Tran22Arnon P. Kater23Mark-David Levin24Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Correspondence: Carsten U. Niemann, Rigshospitalet, Copenhagen University Hospital, Department of Hematology, Building 5074, Blegdamsvej 9, DK-2100 Copenhagen, Denmark;Department of Hematology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsHovon Foundation, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DenmarkDepartment of Hematology, HagaZiekenhuis, Den Haag, The NetherlandsDepartment of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DenmarkDepartment of Hematology, Antonius Ziekenhuis, Sneek, The NetherlandsDepartment of Hematology, Universitair Medisch Centrum Utrecht, Utrecht, The NetherlandsDepartment of Human Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Clinical Genetics, University Medical Center Utrecht, Utrecht, The NetherlandsLaboratory of Special Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Hematology, Zealand University Hospital, Roskilde, DenmarkHovon Foundation, Erasmus MC University Medical Center, Rotterdam, The NetherlandsHovon Foundation, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Hematology, Odense University Hospital, Odense, DenmarkDepartment of Hematology, Universitaire Ziekenhuizen Leuven, Leuven, BelgiumDepartment of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DenmarkDepartment of Hematology, Isala Ziekenhuis, Zwolle, The NetherlandsDepartment of Hematology, Turku University Central Hospital, Turku, FinlandDepartment of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DenmarkDepartment of Hematology, Uppsala University Hospital, Uppsala, SwedenDepartment of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Hematology, Akershus University Hospital, Lørenskog, NorwayHovon Foundation, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The NetherlandsAbstract: Patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) are treated with fixed-duration B-cell lymphoma 2 inhibitors + CD20 monoclonal antibodies or continuous Bruton tyrosine kinase (BTK) inhibitors. Although continuous treatment may lead to cumulative toxicity or resistance, fixed-duration treatment may lead to undertreatment and early relapse. Efficacy and safety of minimal residual disease (MRD)-guided treatment cessation of ibrutinib + venetoclax (I+V) with reinitiated I+V upon MRD conversion was evaluated in the randomized VISION/HO41 phase 2 study. Four-year follow-up including long-term toxicity and MRD kinetics are reported. Patients received ibrutinib for 2 (28-day) cycles followed by 13 cycles of I+V. Patients reaching undetectable MRD at 4 years (<10−4, flow cytometry) in the blood and bone marrow at cycle 15 (C15) were randomized 2:1 between treatment cessation with reinitiated I+V upon detectable MRD2 (dMRD2; sensitivity of ≥10−2 by flow cytometry) and ibrutinib maintenance. MRD4-positive patients at C15 remained on ibrutinib (dMRD4 arm, defined by MRD sensitivity of ≥10−4 by flow cytometry). With a median of 51.7 months, the estimated 4-year overall survival (OS) was 88%, progression free survival (PFS) was 81%; 14% of patients required next-line treatment (NT). For patients randomized to treatment cessation, 40% had reinitiated therapy per protocol because of dMRD2. No difference between treatment cessation, ibrutinib maintenance, or the dMRD4 arm continuing ibrutinib was seen for OS, PFS, or NT in landmark analysis from C15 time of randomization. Lower toxicity was demonstrated for the treatment-cessation arm. MRD-guided cessation and reinitiation of I+V for R/R CLL is feasible, reduces toxicity compared with indefinite BTK inhibitor, while providing comparable PFS rates. This trial was registered at www.clinicaltrials.gov as #NCT03226301.http://www.sciencedirect.com/science/article/pii/S2473952925002381 |
| spellingShingle | Carsten U. Niemann Julie Dubois Kazem Nasserinejad Caspar da Cunha-Bang Sabina Kersting Lisbeth Enggaard Gerrit J. Veldhuis Rogier Mous Clemens H.M. Mellink Anne-Marie F. van der Kevie-Kersemaekers Johan A. Dobber Christian B. Poulsen Wida Razawy René Hollestein Henrik Frederiksen Ann Janssens Ida Schjødt Ellen C. Dompeling Juha Ranti Christian Brieghel Mattias Mattsson Mar Bellido Hoa T. T. Tran Arnon P. Kater Mark-David Levin Long-term follow-up of MRD-guided ibrutinib plus venetoclax in relapsed CLL: phase 2 VISION/HO141 trial Blood Advances |
| title | Long-term follow-up of MRD-guided ibrutinib plus venetoclax in relapsed CLL: phase 2 VISION/HO141 trial |
| title_full | Long-term follow-up of MRD-guided ibrutinib plus venetoclax in relapsed CLL: phase 2 VISION/HO141 trial |
| title_fullStr | Long-term follow-up of MRD-guided ibrutinib plus venetoclax in relapsed CLL: phase 2 VISION/HO141 trial |
| title_full_unstemmed | Long-term follow-up of MRD-guided ibrutinib plus venetoclax in relapsed CLL: phase 2 VISION/HO141 trial |
| title_short | Long-term follow-up of MRD-guided ibrutinib plus venetoclax in relapsed CLL: phase 2 VISION/HO141 trial |
| title_sort | long term follow up of mrd guided ibrutinib plus venetoclax in relapsed cll phase 2 vision ho141 trial |
| url | http://www.sciencedirect.com/science/article/pii/S2473952925002381 |
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