System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ahead of print

PubMed: 42827117 DOI: 10.1038/s41375-026-03150-7

First-line ibrutinib-venetoclax in chronic lymphocytic leukemia: GLOW 67-month results and grade 3/4 adverse event-free progression-free survival.

Leukemia

Authors: Carsten U Niemann, Talha Munir, Carolyn Owen, George Follows, José-Ángel Hernández-Rivas, Ohad Benjamini, Ann Janssens, Mark-David Levin, Tadeusz Robak, Martin Simkovic, Sergey Voloshin, Vladimir Vorobyev, Loic Ysebaert, Natasha Schuier, Kurt Baeten, Nguyet Tran, Bennett Levitan, Claire Kavanagh, Arnon P Kater

Affiliations

  • Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • St James's University Hospital, Leeds, UK.
  • Tom Baker Cancer Centre, Calgary, AB, Canada.
  • Addenbrookes Hospital, Cambridge, UK.
  • Hospital Universitario Infanta Leonor, Universidad Complutense, Madrid, Spain.
  • Sheba Medical Center, Ramat Gan, Israel.
  • Universitaire Ziekenhuizen Leuven, Leuven, Belgium.
  • Albert Schweitzer Hospital, Dordrecht, Netherlands.
  • Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.
  • 4th Department of Internal Medicine-Haematology, Faculty of Medicine in Hradec Králové, University Hospital and Charles University in Prague, Hradec Králové, Czechia.
  • Russian Scientific and Research Institute of Hematology and Transfusiology, St, Petersburg, Russia.
  • S.P. Botkin Moscow City Clinical Hospital, Moscow, Russia.
  • Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France.
  • Johnson & Johnson, Zug, Switzerland.
  • Johnson & Johnson, Beerse, Belgium.
  • Johnson & Johnson, Titusville, NJ, USA.
  • Johnson & Johnson, Dublin, Ireland.
  • Amsterdam University Medical Centers, Cancer Center Amsterdam, University of Amsterdam, HOVON foundation, Amsterdam, Netherlands.

Abstract

Long-term efficacy and toxicity data are needed to inform optimal first-line treatment for individual patients with chronic lymphocytic leukemia (CLL). We report long-term outcomes of ibrutinib-venetoclax in older/comorbid patients at 67-month median follow-up of the phase III GLOW study (NCT03462719) and report grade 3/4 treatment-emergent adverse event (TEAE)-free progression-free survival (PFS). Patients were randomized 1:1 to ibrutinib-venetoclax (n = 106) or chlorambucil-obinutuzumab (n = 105). Sixty-six-month overall survival (OS) rates were 79.0% and 60.8% for ibrutinib-venetoclax and chlorambucil-obinutuzumab, respectively (hazard ratio [HR] 0.46). Ibrutinib-venetoclax reduced the risk of requiring second-line therapy by 77.4% and continued to improve PFS vs chlorambucil-obinutuzumab (66-month rates: 51.7% vs 18.1%, HR 0.27), regardless of IGHV/measurable residual disease (MRD) status. Ibrutinib-venetoclax-treated patients with undetectable MRD at end-of-treatment had better PFS outcomes than those with detectable MRD, especially in patients with unmutated IGHV. Grade 3/4 TEAE-free PFS was 21.4 months longer for ibrutinib-venetoclax vs chlorambucil-obinutuzumab (51.6 vs 30.2 months). Ibrutinib-venetoclax maintains superior OS, superior PFS, reduction in need for second-line treatment, and longer PFS duration without grade 3/4 TEAEs vs chlorambucil-obinutuzumab. Fixed-duration ibrutinib-venetoclax is an effective first-line treatment option for older/comorbid patients with previously untreated CLL, providing durable disease control and preserving future treatment options.

MeSH

Disease-Free Survival, Progression-Free Survival, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Leukemia, Lymphoid, Drug-Related Side Effects And Adverse Reactions, Chlorambucil, Therapeutics