Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Application of High-Sensitivity Troponin in Suspected Myocardial Infarction

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Long-Term Outcomes of Partial Oral Treatment of Endocarditis

    Research output: Contribution to journalJournal articleResearch

  3. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Epidemiology of bloodstream infections in patients with chronic lymphocytic leukemia: a longitudinal nation-wide cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Targeting Bruton's Tyrosine Kinase Across B-Cell Malignancies

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Kirsten Fischer
  • Othman Al-Sawaf
  • Jasmin Bahlo
  • Anna-Maria Fink
  • Maneesh Tandon
  • Mark Dixon
  • Sandra Robrecht
  • Simon Warburton
  • Kathryn Humphrey
  • Olga Samoylova
  • Anna M Liberati
  • Javier Pinilla-Ibarz
  • Stephen Opat
  • Liliya Sivcheva
  • Katell Le Dû
  • Laura M Fogliatto
  • Carsten U Niemann
  • Robert Weinkove
  • Sue Robinson
  • Thomas J Kipps
  • Sebastian Boettcher
  • Eugen Tausch
  • Rod Humerickhouse
  • Barbara Eichhorst
  • Clemens-Martin Wendtner
  • Anton W Langerak
  • Karl-Anton Kreuzer
  • Matthias Ritgen
  • Valentin Goede
  • Stephan Stilgenbauer
  • Mehrdad Mobasher
  • Michael Hallek
View graph of relations

BACKGROUND: The BCL2 inhibitor venetoclax has shown activity in patients with chronic lymphocytic leukemia (CLL), but its efficacy in combination with other agents in patients with CLL and coexisting conditions is not known.

METHODS: In this open-label, phase 3 trial, we investigated fixed-duration treatment with venetoclax and obinutuzumab in patients with previously untreated CLL and coexisting conditions. Patients with a score of greater than 6 on the Cumulative Illness Rating Scale (scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or a calculated creatinine clearance of less than 70 ml per minute were randomly assigned to receive venetoclax-obinutuzumab or chlorambucil-obinutuzumab. The primary end point was investigator-assessed progression-free survival. The safety of each regimen was also evaluated.

RESULTS: In total, 432 patients (median age, 72 years; median Cumulative Illness Rating Scale score, 8; median creatinine clearance, 66.4 ml per minute) underwent randomization, with 216 assigned to each group. After a median follow-up of 28.1 months, 30 primary end-point events (disease progression or death) had occurred in the venetoclax-obinutuzumab group and 77 had occurred in the chlorambucil-obinutuzumab group (hazard ratio, 0.35; 95% confidence interval [CI], 0.23 to 0.53; P<0.001). The Kaplan-Meier estimate of the percentage of patients with progression-free survival at 24 months was significantly higher in the venetoclax-obinutuzumab group than in the chlorambucil-obinutuzumab group: 88.2% (95% CI, 83.7 to 92.6) as compared with 64.1% (95% CI, 57.4 to 70.8). This benefit was also observed in patients with TP53 deletion, mutation, or both and in patients with unmutated immunoglobulin heavy-chain genes. Grade 3 or 4 neutropenia occurred in 52.8% of patients in the venetoclax-obinutuzumab group and in 48.1% of patients in the chlorambucil-obinutuzumab group, and grade 3 or 4 infections occurred in 17.5% and 15.0%, respectively. All-cause mortality was 9.3% in the venetoclax-obinutuzumab group and 7.9% in the chlorambucil-obinutuzumab group. These differences were not significant.

CONCLUSIONS: Among patients with untreated CLL and coexisting conditions, venetoclax-obinutuzumab was associated with longer progression-free survival than chlorambucil-obinutuzumab. (Funded by F. Hoffmann-La Roche and AbbVie; ClinicalTrials.gov number, NCT02242942.).

Original languageEnglish
JournalThe New England journal of medicine
Volume380
Issue number23
Pages (from-to)2225-2236
Number of pages12
ISSN0028-4793
DOIs
Publication statusPublished - 6 Jun 2019

    Research areas

  • Aged, Antibodies, Monoclonal, Humanized/administration & dosage, Antineoplastic Agents, Immunological/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Bridged Bicyclo Compounds, Heterocyclic/administration & dosage, Chlorambucil/administration & dosage, Comorbidity, Female, Humans, Kaplan-Meier Estimate, Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy, Male, Progression-Free Survival, Sulfonamides/administration & dosage

ID: 57444084